Nodular Erythema Elevatum Diutinum Mimicking Kaposi's Sarcoma in a Human Immunodeficiency Virus Infected Patient

Erythema elevatum diutinum (EED) has been emerging as a specific Human Immunodeficiency Virus (HIV) associated dermatosis in recent times. It is an extremely rare chronic disease of unknown origin and part of the spectrum of leukocytoclastic vasculitis. We describe a case of EED simulating Kaposi''s sarcoma in a 52-year-old HIV infected female patient with no previous opportunistic infections and CD4+ count of 164/mm³. Therapy with oral dapsone (100 mg/day) for two weeks resulted in resolution of some lesions.     

Erythema elevatum et diutinum

Erythema elevatum et diutinum (EED) is a rare, chronic, cutaneous, leukocytoclastic vasculitis. It is characterized by symmetric, plaques, papules and nodules occurring preferentially on the extensor aspects of the arms. An association with chronic infections, neoplasms, especially myeloproliferative diseases and paraproteinemia, as well as autoimmune disorders (rheumatoid arthritis, Crohn disease) has been described. An 83-year-old woman with EED presented with symmetric, skin colored, firm nodules on the extensor surfaces of her fingers for two years. This case report summarizes the central clinical aspects and differential diagnosis of EED as well as its therapeutic options.     

持久性隆起性红斑伴再生障碍性贫血一例并文献复习

持久性隆起性红斑(erythema elevatum diutinum, EED)是一种罕见的皮肤白细胞破碎性血管炎,其病因不明确,认为与感染、血液系统疾病、自身免疫性疾病感染的循环免疫复合物在血管壁沉积有关,因此除单纯的皮肤表现外,既往报道39.4%的EED伴发HIV、病毒性肝炎、链球菌感染、副蛋白血症、骨髓增生异常综合征、系统性红斑狼疮和类风湿性关节炎等疾病。现报道我院诊治的持久性隆起性红斑伴再生障碍性贫血一例,并通过文献检索,分析伴发其他系统性疾病的EED的临床特征,初步探讨EED与血液系统疾病及恶性肿瘤的关联性。     

Erythema elevatum diutinum: a case report and review of literature

Erythema elevatum diutinum (EED) is a rare cutaneous leukocytoclastic vasculitis thought to be related to increased levels of circulating antibodies. It has been shown to be associated with HIV infection, tuberculosis, as well as various autoimmune diseases. A retrospective review of all cases of EED indexed in PubMed between 1990 and 2014 was performed. Inclusion criteria for articles was availability of full text in English and a biopsy-confirmed diagnosis of EED. All other articles were excluded. Cases were stratified by age and anatomic location of the lesions. Treatment response was coded as “complete,” “partial,” and “none.” A total of 133 cases of EED with 381 lesions detailed in case reports and case series were included. Twenty-one cases were associated with HIV. Of 47 patients with reported paraproteinemias, IgA paraproteinemia was found in 57.45%, IgG paraproteinemia in 29.8%, IgM paraproteinemia in 10.6%, and IgD paraproteinemia in 2.1% of cases. Of 40 (30.1%) patients with reported comorbid autoimmune disease, rheumatoid arthritis was associated with 10 cases. Cancer was found to be associated with 9.77% of cases. Seventy-five patients were treated with dapsone, with 36 (48%) achieving complete treatment response, 24 (32%) achieving partial response, and seven (9.3%) achieving no response. Keeping the clinical associations of EED in mind, especially malignancy, is critical in management of the disease. More structured studies need to take place in order to fully define the mechanisms and strength of these associations.     

Erythema elevatum diutinum in a patient with human immunodeficiency virus

Erythema elevatum diutinum (EED) is a chronic cutaneous leukocytoclastic vasculitis. This rare disease is characterized by red, brownish-purple, and yellow papules, plaques, and nodules distributed symmetrically about the extremities. There have been recent reports of the disease in association with infection with the human immunodeficiency virus (HIV). We describe the case of a 51-year-old man with HIV who presented with EED, which was successfully treated with dapsone.     

Sulfone therapy in the treatment of leukocytoclastic vasculitis. Report of three cases

Dapsone therapy for leukocytoclastic (necrotizing) vasculitis has been little used, except for the variant forms of erythema elevatum diutinum and urticarial vasculitis. We report three patients with the common (palpable purpura) form of the disease, limited to the skin, and successfully treated with moderate doses of dapsone (100-150 mg daily). Although the natural course of leukocytoclastic vasculitis is highly unpredictable, the prompt disappearance of new lesion formation after initiation of treatment and the rapid recurrence of lesions after therapy is discontinued (both often within 4 to 8 days after the critical dose level is reached) reflect drug efficacy. We believe that dapsone deserves wider evaluation as a therapeutic agent for chronic or recurrent cases of the common form of leukocytoclastic vasculitis.     

The evolution of lesions in erythema elevatum diutinum

We obtained biopsies from early, fully developed, and late lesions of erythema elevatum diutinum (EED) in a 49-year-old man. The histologic and electron-microscopic findings were compared with those reported in the literature and three other cases from our files. Early lesions show leukocytoclastic vasculitis with capillary proliferation. Later lesions show vasculitis, dermal aggregates of neutrophils, fibrosis, and areas of granulation tissue. Newly formed vessels in granulation tissue may be more susceptible to damage by immune complexes, and the early formation of granulation tissue in EED may prevent an early resolution of vasculitis. Damage to dermal connective tissue in EED incites either scarring or, rarely, a fibrohistiocytic proliferation. Ultrastructural examination of one case showed histiocytes with myelin figures and intracellular lipid and cholesterol.     

Erythema elevatum diutinum in a patient with acquired immunodeficiency syndrome. Another clinical simulator of Kaposi's sarcoma.

Several types of vasculitis have been described in patients with human immunodeficiency virus infection. Erythema elevatum diutinum is a rare variant of cutaneous leukocytoclastic vasculitis which, with the exception of the case reported herein, has been described only once in human immunodeficiency virus-infected patients. Our male patient, a longtime intravenous drug abuser, had cutaneous lesions, closely resembling Kaposi's sarcoma, on the extensor surfaces of the lower extremities. Cutaneous biopsy specimens, however, demonstrated leukocytoclastic vasculitis with fibrinoid necrosis of the vessel walls and areas of basophilic degeneration of collagen bundles in early lesions, whereas late lesions showed dense diffuse fibrosis with proliferation of dermal spindle cells and some foci of residual leukocytoclastic vasculitis. Oral therapy with dapsone resulted in marked clearing of the cutaneous lesions within few days. This case raises the necessity of histologic confirmation for all cases of suspected Kaposi's sarcoma in patients with acquired immunodeficiency syndrome. We discuss the possible pathogenesis of leukocytoclastic vasculitis in human immunodeficiency virus-infected patients.     

Erythema elevatum diutinum: an "idiopathic" case

Erythema elevatum diutinum (EED) is a rare condition with an unclear pathogenesis. Initially classified within neutrophilic dermatoses, it is now considered as a leukocytoclastic vasculitis accordingly to its histopathologic pattern. Several clinical presentations as well as many associated diseases are reported in the literature. We report a new case of EED in a 58-year-old man who presented with a three-month history of plaques and nodules on the extensor surfaces of hands, elbows, knees, ankles, forearms, and buttocks. Histology showed a leucocytoclastic vasculitis, suggestive of the diagnosis of EED. Screening for an associated pathology, namely a paraproteinemia or a solid cancer, was negative. Treatment with dapsone leads to amelioration within few weeks.     

Erythema elevatum diutinum--evidence for disease-dependent leucocyte alterations and response to dapsone

Erythema elevatum diutinum (EED) is a type of leucocytoclastic vasculitis of unknown aetiology. We report a patient with unusually widespread and disabling EED that had been unresponsive to corticosteroids and antibiotics, but resolved on dapsone. Biopsies of fresh lesions showed typical features of leucocytoclastic vasculitis, with prominent neutrophil infiltration, marked expression of the beta(2)-integrins CR3 and LFA-1, and increased mast cell numbers. Older lesions exhibited granulation tissue and fibrosis, macrophages were more dominant, beta(2)-integrins were expressed less markedly, and mast cell numbers were lower. In vitro chemotaxis of the patient's peripheral blood neutrophils prior to treatment showed increased random migration and directed migration towards interleukin-8 (by 424%), but a profoundly decreased responsiveness towards the bacterial peptide analogue N-formyl-methionyl-leucyl-phenylalanine (fMLP) (by 98%). These values returned to normal after dapsone treatment and clinical improvement 5 months later. These findings support the concept that in EED, activation via cytokines such as interleukin-8 allows a selective recruitment of leucocytes to tissue sites, while immune complexes and bacterial peptides sustain the persistent local inflammatory infiltrate and the leucocytoclastic vasculitis.     

Acute febrile neutrophilic dermatosis (Sweet's syndrome). Association with rheumatoid vasculitis

A 58-year-old woman suffering from rheumatoid arthritis complicated by a leukocytoclastic vasculitis had an acute febrile neutrophilic dermatosis (Sweet's syndrome) develop immediately after worsening of her arthritic condition. This association supports the hypothesis that immunologic abnormality is involved in the pathogenesis of Sweet's syndrome and raises the question of a possible common pathogenic pathway between neutrophilic dermatoses and leukocytoclastic vasculitis.     

Factor XIIIa+ dermal dendrocytes in erythema elevatum diutinum and ordinary cutaneous leukocytoclastic vasculitis lesions

Factor XIIIa+ dermal dendrocytes belong to the dermal microvascular unit and are related to wound healing, angiogenic and fibrogenic processes. Erythema elevatum diutinum (EED) is a leukocytoclastic vasculitis followed by repair and fibrosis. In order to verify the involvement of fXIIIa+DD in the pathogenesis of EED and ordinary leukocytoclastic vasculitis (OLV) these cells were immune labeled with anti-factor XIIIa antibody and quantified in 15 biopsies of EED, 18 of OLV and compared with 11 fragments of normal skin (NS). The number of vessels was evaluated by endothelial cell staining with anti CD34 antibody. FXIIIa+DD appeared in both groups of vasculitis with hyperthophic dendrites, with no difference in their number at any level of the dermis. The number of fXIIIa+DD in the superficial dermis was higher in OLV than in NS (p<0.001). The number of dermal vessels in the EED group was higher at all dermis depths evaluated when compared with NS (p<0.05) and in the middle and deep dermis when compared with OLV (p<0.05). The results suggest the participation of fXIIIa+DD in the immunopathological mechanisms of both groups of vasculitis studied. However, there was no correlation between the number of fXIIIa+DD and angiogenesis and fibrogenesis in the EED lesions.     

Histamine-triggered localized vasculitis in patients with seropositive rheumatoid arthritis

To gain some insight into the pathogenesis of vasculitis in rheumatoid arthritis, and to investigate its relation to circulating immunoreactants, we injected 50 microliters of histamine intradermally in four seropositive and four seronegative patients with rheumatoid arthritis. Skin biopsies obtained before histamine and at 4 hours after histamine were studied by immunofluorescence microscopy, and skin biopsies 24 hours after histamine were studied by light microscopy. At 4 hours after histamine, all seropositive patients demonstrated deposits of IgM and complement components in dermal vessels; by 24 hours, various degrees of leukocytoclastic vasculitis were noted. Circulating material reactive with Raji cells, C1q, or both, was present in 3/3 seropositive patients. In contrast, none of the seronegative patients exhibited vascular deposits of immunoreactants or vasculitis. The results indicate that patients with rheumatoid arthritis who are seropositive may have circulating complexes with appropriate characteristics to induce vasculitis and that vasoactive substances may be used to trigger their local deposition in vessels.     

Pustular vasculitis disclosing a systemic lupus erythematosus

Pustular lesions on purpuric bases with histologic characteristics of leukocytoclastic vasculitis have been identified as a distinct condition. They were first described in relation to Behçet's syndrome, bowel × associated dermatosis–arthritis syndrome, or chronic gonococcemia. ^1,2 In recent years, this variety of vasculitis has been associated with other diseases, ³ but, to our knowledge, not with lupus erythematosus.     

Late-stage nodular erythema elevatum diutinum

Erythema elevatum diutinum (EED) is a rare chronic vasculitic process of unknown etiology that presents as bilateral, symmetrical, periarticular, red-brown papules and plaques, often over dorsa of joints. Early histologic changes are characterized by leukocytoclastic vasculitis. With chronicity, the lesions develop dense neutrophilic infiltrate and fibrosis. We describe an unusual case of late-stage nodular EED present for 35 years in a seronegative 75-year-old man. Asymptomatic papules and plaques measuring from 0.7 to 9.0 cm were seen over the interphalangeal joints, elbows, knees, and ankles. The histologic findings were characterized by predominant concentric fibrosis that formed well-circumscribed dermal and subcutaneous nodules. Awareness of this unusual presentation of EED helps to avoid misdiagnosis as cutaneous neoplasms.     

Annular lesions of cutaneous sarcoidosis with granulomatous vasculitis

Sarcoidosis is known to be involved in diseases with vasculitis as sarcoid vasculitis. However, vasculitis in cutaneous sarcoidal lesions is extremely rare. Here we describe a case of sarcoidosis with multiple annular skin lesions with granulomatous vasculitis. A 62‐year‐old female was diagnosed with sarcoidosis by chest‐abdominal computed tomographic examination and laboratory tests. The skin lesions had appeared on her lower limbs 2 years before. Physical examination showed multiple infiltrated annular eruptions on the lower extremities. A skin biopsy of an area of erythema showed multiple non‐caseating epithelioid cell granulomas in the dermis and subcutaneous fat and granulomatous vasculitis with fibrinoid degeneration in the subcutaneous fat. There are two types of vasculitis in sarcoidosis: leukocytoclastic and granulomatous vasculitis. Ulcers and livedo were more common in granulomatous vasculitis than in leukocytoclastic vasculitis. The present case had unique annular skin lesions of sarcoidosis with granulomatous vasculitis.     

Palisaded neutrophilic granulomatous dermatitis in rheumatoid arthritis

Palisaded neutrophilic granulomatous dermatitis (PNGD) is an entity that has not been clearly defined either clinically or histopathologically. It is seen in patients with rheumatoid arthritis and other connective tissue diseases. In the past, many cases of PNGD have been described under several different names including palisaded neutrophilic and granulomatous dermatitis, linear subcutaneous bands, interstitial granulomatous dermatitis with cutaneous cords and arthritis, rheumatoid papules, and Churg-Strauss granuloma. We report 7 additional cases of PNGD. Clinically, 6 patients presented with erythematous to violaceous plaques, papules, and nodules on multiple body sites; one presented with subcutaneous linear bands on the shoulder. Five had rheumatoid arthritis; one had adult-onset Still's disease; and one showed clinical signs of rheumatoid arthritis, although serologically the rheumatoid factor was negative. On histologic examination, a spectrum of changes was observed ranging from urticaria-like infiltrates to leukocytoclastic vasculitis and granuloma annulare with neutrophils. We report these cases to expand the histologic spectrum of this entity and to further delineate the different forms of clinical presentation.     

Multiple rheumatoid papules characteristic of the early stage of rheumatoid vasculitis.

The rheumatoid papule has recently been described as the skin manifestation of rheumatoid arthritis (RA). The papules represent leukocytoclastic vasculitis and necrobiosis clinicopathologically. We report a 59-year-old Japanese woman with multiple recurrent rheumatoid papules located on the bilateral extensor forearms in correlation with the level of RA activity and as a cutaneous manifestation of rheumatoid vasculitis. These papules appeared prior to other cutaneous manifestations. It was suggested that rheumatoid papules represent the early stage of rheumatoid vasculitis and that they are a reliable early clinical marker of rheumatoid vasculitis.     

Granuloma faciale with extrafacial lesions

Extrafacial involvement in granuloma faciale (GF) is rather exceptional. We report herein a patient with GF associated with lesions on the trunk and the forearm. Histological studies of facial and extrafacial lesions shared similar characteristics: a mixed inflammatory infiltrate with abundant eosinophils in the superficial and middle dermis with a narrow grenz zone of uninvolved dermis between the epidermis and the infiltrate. Evidence of vasculitis was clearly observed in both biopsy specimens. Treatment with dapsone did not alter the course of the disease. We review the 12 cases of extrafacial GF that have been reported in the English and Spanish literature. In these cases a diagnosis of erythema elevatum diutinum (EED) may be suggested. Although GF and EED may share some pathogenic mechanisms, there are several clinical and histological differences between them that make us consider EED and GF as distinct entities.     

氨苯砜单疗治疗类风湿性嗜中性皮炎一例

类风湿性嗜中性皮炎是一种严重类风湿关节炎的特异性皮肤表现,本文报道一例并复习相关文献。患者,男,60岁。躯干、四肢泛发暗红色丘疹、水疱1个月,类风湿关节炎病史7年。实验室检查及组织病理符合类风湿性嗜中性皮炎。患者因类风湿关节炎病史曾使用免疫抑制剂和糖皮质激素,本次选择氨苯砜单疗,治疗2周后实验室检查异常项目恢复正常,皮损明显消退。