HistoryThis section has been translated automatically.
Hutchinson 1888; Bury 1889; Radcliffe-Crocker & Williams 1894. Erythema elevatum et diutinum (EED) was first described in the 1880s. The term "erythema elevatum diutinum" was first used by Henry Radcliffe-Crocker (1845-1909) in 1894.
DefinitionThis section has been translated automatically.
Relatively rare (less than 1000 cases have been described in the literature worldwide), benign, albeit eminently chronic (diutinum!), reactive-inflammatory disease of the skin with the characteristic histologic picture of leukocytoclastic "small vessel" vasculitis with consecutive angiocentric and storiform fibrosis (Sandhu JK et al. 2019).
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Occurrence/EpidemiologyThis section has been translated automatically.
Relatively rare, epidemiology figures are not available.
EtiopathogenesisThis section has been translated automatically.
Unexplained, probably "immune-triggered " vasculitis of small vessels; occasional detection of monoclonal immunoglobulins, most commonly in the setting of IgA gammopathy (less commonly IgG gammopathy/multiplemyeloma), possibly also in cryoglobulinemia.
Clinical symptoms are thought to be due to deposition of immune complexes in skin blood vessels, leading to complement fixation, activation of the complement system, influx of neutrophils, and release of destructive enzymes.
Apparently, antineutrophil cytoplasmic antibodies (ANCAs) could be pathogenetically active in EED. They are detected in a high percentage of diseased individuals (Ayoub N et al 2004). Furthermore, EED may be triggered by the activation of cytokines (interleukin-8) that cause selective recruitment of leukocytes into blood vessels. This leads to repeated damage to the vessels, which eventually develops into fibrosis.
Associations with infections (e.g. HIV, hepatitis B,hepatitis C, HIV), with autoimmune diseases, especially rheumatoid arthritis, as well as Crohn 's disease, ulcerative colitis, Wegener's granulomatosis have been described; furthermore with myelodysplasias. The occurrence of EED after COVID vaccination has been reported many times (Fiorillo G et al. 2022).
The presence of extracutaneous manifestations (see below) in patients with erythema elevatum diutinum (EED) suggests that EED may be a multiorgan vasculitic systemic disease.
ManifestationThis section has been translated automatically.
LocalizationThis section has been translated automatically.
Mainly over the extensor sides of the extremity joints (fingers, hands, knees), also buttocks, genitals, face and neck.
Clinical featuresThis section has been translated automatically.
Subacute development of symmetrically arranged, initially soft, later firm, roundish, also anular or polycyclic, blue-red or red-brown, also hemorrhagic, succulent plaques over a large area (Note: A purpuric component is not always clearly evident, since the small focal hemorrhages occur episodically). In the course of weeks and months, blue-red-brown, surface-smooth, firm, broad-based, several centimeter large nodules may develop. Central indentation can be frequently detected, possibly also stabbing pain, burning or itching. Early lesions tend to be bright red, whereas older lesions tend to be livid red to brownish red. EED in dark skin presents a particular clinical challenge because the initial red tones are now completely obscured and only the slightly darker tinged, plaque or nodular contouring is recognizable.
Plate-like, keloid lesions are also described. These are apparently completely resistant to therapy, so that surgical methods also become necessary (Awan BE et al. 2021/s.Fig.).
Possible syntropias exist with gout, arthralgias, scleritis, panuveitis, peripheral ulcerative keratitis, with Sjögren's syndrome (Shimizu S et al 2008), oral and penile ulcers (Sandhu JK et al 2019). Evidence suggests early indications of non-Hodgkin's lymphoma (Hatzitolios A et al 2008). The extent to which pathogenetic links exist to the clinical picture of "pulmonary hyaline granulomatosis" is currently unclear (see Rodríguez-Muguruza S et al. 2015; see also Müller CSL et al. 2009). The skin lesions may heal after years (periods of 5-35 years are reported) leaving hyperpigmented scars.
HistologyThis section has been translated automatically.
At an early stage, the signs of leukocytoclastic vasculitis can be detected with perivascular oriented neutrophilic leukocytes and nuclear dust as well as fibrin in the vessel walls.
In "full-blown" lesions, a dense, diffuse infiltrate is found in the upper and middle dermis. Vascular orientation is then usually not (or no longer) detectable. Epidermis and skin appendages remain uninvolved. The infiltrates consist of lymphocytes, neutrophilic leukocytes and nuclear dust, eosinophilic leukocytes, histiocytes and plasma cells. In addition, proliferation of fibrocytes as well as collagen fibers. Concentric fibrosis may dominate the fine tissue picture in older lesions, possibly with a "pseudotumorous" aspect. Also in older lesions, lipid deposits can be detected in the connective tissue, which gave the clinical picture the name "extracellular cholesterolosis" at that time (Herzberg JJ 1958; Wolff HH et al. 1978). Their pathogenetic significance is unclear.
Schematizingly, the following algorithm can be established:
|Accentuated around postcapillary venules|
|capillaries left out of the less involved|
|Damage to endothelial cells|
|Fibrin in/in the area of vessel walls|
|perivascular extravasation of erythrocytes|
|Edema in the papillary dermis|
|Variable number of eosinophils|
Plasma cells and fibrosclerosis
Note: In older lesions, increasing concentric fibrosis with regression of the inflammatory component of the granulomatous reaction.
Differential diagnosisThis section has been translated automatically.
Granuloma anulare: the greatest clinical analogies exist with this clinical picture. However, the EED shows a stronger inflammation. Histological clarification may be necessary.
Granuloma facale: the classic granuloma faciale has to be excluded due to its localization. The rare extrafacial granuloma "faciale" has to be excluded histologically.
Erythema anulare centrifugum: anular truncal red plaques; no nodularity;
Erythema multiforme: the clinical acuity of EEM speaks absolutely against the protracted course of EED; typical clinical picture with the cocard lesions.
Acute febrile neutrophilic dermatosis (Sweet's sndrome): acute exanthematous, febrile, papulo-pustular clinical picture, laboratory with inflammatory parameters.
Rheumatoid nodules: nodules and nodules belonging to the so-called rheumatism nodosus, occurring in 20% of patients with chronic polyarthritis (rheumatoid arthritis), mostly in severe courses. Rheumatoid factor positive.
Multicentric reticulohistiocytosis: Symmetrically distributed, multiple, pinhead- to pea-sized, mostly derb-consistent, skin-colored but also copper-brown, sometimes slowly growing, sometimes eruptively exanthematous, solitary, also confluent papules and nodules, possibly with atrophic, possibly also excoriated, mostly smooth surface. Typical (>50% of cases) is a pearl cord-like involvement of the nail folds of the fingers (coral bead sign). In 25% of the cases, xanthelasma are present at the same time.
TherapyThis section has been translated automatically.
If necessary, treatment of the underlying disease.
The best results are described with DADPS. Patients respond to varying doses (50-150 mg/day). Improvement is immediate in some patients within days, in others skin lesions take months to heal. Treatment failures are known.
Local therapy with a 5% dapsone gel (ACZONE; Allergan Inc, Irvine, CA/Frieling GW et al. 2013) also appears to be effective in isolated cases.
The clinical picture is usually less responsive to glucocorticoids. However, a therapy cycle over 4-6 weeks is recommended (initially 50mg prednisolone /day; gradual reduction over the indicated period) .
The use of nicotinamide (e.g. Nicobion 1 tbl./day) is described as successful in individual cases.
Symptomatic therapy of itching with H 1 antagonists, e.g. desloratadine (Aerius) 1 tablet/day p.o. or levocetirizine (Xusal) 1 tablet/day p.o..
Progression/forecastThis section has been translated automatically.
Chronic course. Spontaneous healing is possible after years, leaving a hypo- or hyperpigmented scar.
LiteratureThis section has been translated automatically.
- Awan BE et al (2021) A Case of Erythema Elevatum Diutinum (EED) Exhibiting A Keloid-Like Appearance. Dermatol Ther (Heidelb) 11:2235-2240.
- Ayoub N et al (2004) Antineutrophil cytoplasmic antibodies of IgA class in neutrophilic dermatoses with emphasis on erythema elevatum diutinum. Arch Dermatol 140:931-936.
- Burnett PE et al (2003) Erythema elevatum diutinum. Dermatol Online J 9: 37
- Bury JS (1889) A case of erythema with remarkable nodular thickening and induration of the skin associated with intermittent albuminuria. Illus Med News 3: 145
- Chen KR et al (2002) Clinical and histopathological spectrum of cutaneous vasculitis in rheumatoid arthritis. Br J Dermatol 147: 905-913.
- Frieling GW et al (2013) Novel use of topical dapsone 5% gel for erythema elevatum diutinum: safer and effective. J Drugs Dermatol. 12:481-484.
- Fiorillo G et al. (2022) New-onset erythema elevatum diutinum following COVID-19 vaccination. Ital J Dermatol Venerol 157:527-528.
- Hatzitolios A et al. (2008) Erythema elevatum diutinum with rare distribution as a first clinical sign of non-Hodgkin's lymphoma: a novel association? J Dermatol 35:297-300.
- Herzberg JJ (1958) Extracellular cholesterinosis (KERL-URBACH), a variant of erythema elevatum diutinum. Archives of clinical and experimental dermatology 205: 477-496.
- High WA et al (2003) Late-stage nodular erythema elevatum diutinum. J Am Acad Dermatol 49: 764-767.
- Hoy JV et al (2018) Unusual presentation of erythema elevatum diutinum with underlying hepatitis B infection. Cutis101:462-465.
- Hutchinson J (1888) On two remarkable cases of symmetrical purple congestion of the skin in patches, with induration. Br J Dermatol 1: 10-15
- Kim H (2003) Erythema elevatum diutinum in an HIV-positive patient. J Drugs Dermatol 2:411-412.
- Lisi S et al (2003) A case of erythema elevatum diutinum associated with antiphospholipid antibodies. J Am Acad Dermatol 49: 963-964.
- Liu J et al (2022) Erythema elevatum diutinum. Am J Med Sci 363:e21-e22.Liu J et al. (2022) Erythema Elevatum Diutinum. Am J Med Sci 363:e21-e22.
- Mançano VS et al (2018) Erythema elevatum diutinum. An Bras Dermatol. 2018 Jul-Aug;93(4):614-615.
- Manni E et al. (2014) Case of erythema elevatum diutinum associated with IgA paraproteinemia successfully controlled with thalidomide and plasma exchange. Ther Apher Dial 19:195-196
- Momen SE egt al. (2014) Erythema elevatum diutinum: a review of presentation and treatment. J Eur Acad Dermatol Venereol 28:1594-1602.
- Müller CSL et al (2009) Erythema elevatum et diutinum associated with pulmonary infiltrates and necrotizing keratopathy - a diagnostic challenge! Current Dermatology 35: 502 - 505
- Patnala GP et al (2016) Erythema elevatum diutinum in association with IgA monoclonal gammopathy: A rare case report. Indian Dermatol Online J. 7:300-303.
- Radcliffe-Crocker HW, Williams C (1894) Erythema elevatum diutinum. Br J Dermatol 6: 1-9 u. 53-5.
- Ratzinger G et al (2015) The vasculitis wheel-an algorithmic approach to cutaneous vasculitides. JDDG 1092-1118
- Rodríguez-Muguruza S et al (2015) Pulmonary hyalinizing granuloma associated with Sjögren syndrome and ANCA MPO vasculitis. Joint Bone Spine 82:71-72.
- Sandhu JK et al (2019) Erythema elevatum et diutinum as a systemic disease. Clin Dermatol 37:679-683.
- Shimizu S et al (2008) Erythema elevatum diutinum with primary Sjögren syndrome associated with IgA antineutrophil cytoplasmic antibody. Br J Dermatol 159:733-735
- Wolff HH et al (1978) Erythema elevatum diutinum. I. Electron microscopy of a case with extracellular cholesterolosis. Arch Dermatol Res 15:261:7-16.
- Wollina U et al. (2022) Severe leukocytoclastivc vasculitis after COVID-19 vaccination-cause or coincidence? Case reprot and literature review. Georgian Med News 324:134-139.
Incoming links (18)Cholesterol, extracellular; Crocker, radcliffe henry; Cryoglobulins and skin; Dadps; Dermatitis-arthritis syndromes; Erythema; Erythema figuratum perstans; Erythema microgyratum persistens; Granulomatous interstitial Dermatitis with arthritis; Hutchinson, jonathan; ... Show all
Outgoing links (24)Antihistamines; Cholesterol, extracellular; Crohn disease, skin alterations; Cryoglobulins and skin; Dadps; Desloratadine; Erythema anulare centrifugum; Erythema multiforme; Facial granuloma; Glucocorticosteroids systemic; ... Show all
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