For histopathology see Figure 165-5.
Histopathologic findings are predominantly those of a chronic LCV, with thickening of blood vessel walls, mural and luminal neutrophilia, vascular occlusion, fibrinoid necrosis of vessel walls, endothelial cell swelling, leukocytoclasia, and dermal neutrophilia with lymphocytes (Fig. 165-5). Epidermal changes of hyperkeratosis, acanthosis, ulceration, subepidermal edema, and bulla formation may also be observed.1,3,16
The histopathologic features characteristic for EED are not usually all present within the same lesion. There is an evolution of the pathologic features that can be seen with progression from the early stages into the later stages of disease.
Early stage lesions are characterized by leukocytoclastic vasculitis with a moderately dense perivascular inflammatory infiltrate consisting of neutrophils, leukocytoclastic debris, macrophages, and histiocytes (see eFig. 165-5.1). Fibrin deposition is also evident within the vascular walls. At this stage, the histologic differential diagnosis is broad and includes all the potential causes of LCV. However, the histologic features of EED at this early stage may mimic those of dermatitis herpetiformis. The distinguishing feature for dermatitis herpetiformis includes a limitation of the neutrophilic infiltrate to the papillary dermis, whereas in EED the infiltrate tends to be more diffuse. Other entities to consider in the differential diagnosis include the neutrophilic dermatoses, such as Sweet syndrome, bowel bypass syndrome, and rheumatoid neutrophilic dermatitis, none of which has LCV as a predominant feature.17 Clinicopathologic correlation is necessary to establish the diagnosis in the early stages of disease.
Higher magnification from Fig. 166-5 highlighting the early granulation tissue-like response.
With progression of disease, a granulation tissue-like response with fibroplasia and capillary proliferation becomes the predominant feature1,3 (see eFigs. 165-5.1 and 165-5.2). The infiltrate is increasingly composed mostly of histiocytes, some with phagocytosed nuclear debris. At this stage, the histopathologic features (see eFig. 165-5.3) may be indistinguishable from other fibrosing lesions, such as a solitary sclerotic fibroma, fibrous histiocytomas, and dermatofibrosarcoma protuberans, or vascular lesions such as pyogenic granuloma, Kaposi sarcoma, and bacillary angiomatosis.1,17,18 In the later stages of disease, xanthomatization is occasionally observed. This is characterized by the presence of both intra- and extracellular cholesterol deposits within infiltrating histiocytes and the dermis as demonstrated by ultrastructural studies.1,19
Later-stage lesion of erythema elevatum diutinum. Prominent perivascular and interstitial fibrosis with scattered lymphocytes and histiocytes. Marked stromal fibrosis.
End-stage lesion of erythema elevatum diutinum. Concentric perivascular fibrosis and interstitial fibrosis with lymphocytes and histiocytes.
Direct immunofluorescence findings of lesional skin are generally nondiagnostic and range from few to many blood vessels within the superficial to middermis, with variable staining with various conjugates, including IgG, IgM, C3, and fibrinogen.14,20
Other Laboratory Findings
Table 165-1 Associated Entities ||Download (.pdf)
Table 165-1 Associated Entities
Connective Tissue Diseases/Autoimmune Conditions
Chronic bacterial infections
Cutaneous lupus erythematosus
Human herpesvirus 6
IgA/IgG paraproteinemia (monoclonal gammopathy/MGUS/myeloma)
Systemic lupus erythematosus
Insulin-dependent diabetes mellitus
Streptococcal infection/rheumatic fever
Chronic lymphocytic leukemia
Hyperimmunoglobulinemia D syndrome
Lymphadenopathy-associated virus/human T-cell lymphotrophic virus type 3
Autoimmune keratolysis of the eye
Hemophilia Peripheral ulcerative keratitis
Pulmonary lymphoepithelioma-like carcinoma22