Hypereosinophilic syndrome presenting as cutaneous necrotizing eosinophilic vasculitis and Raynaud's phenomenon complicated by digital gangrene

Cutaneous necrotizing eosinophilic vasculitis is a recently identified type of vasculitis that is characterized by an eosinophil-predominant necrotizing vasculitis affecting small dermal vessels. Clinically, it presents with pruritic erythematous and purpuric papules and plaques, peripheral eosinophilia and a good response to systemic steroid therapy. This vasculitis can be idiopathic or associated with connective tissue diseases. Although the pathogenic roles of eosinophil-derived granule proteins and interleukins have been documented in diseases associated with eosinophilia, a role of CD40 (a glycoprotein of the tumour necrosis factor receptor superfamily) has rarely been described. We describe two patients with idiopathic hypereosinophilic syndrome (HES) presenting with multiple erythematous patches and plaques on the lower extremities and Raynaud's phenomenon. They satisfied the criteria for the diagnosis of HES by clinical and laboratory investigations. Histopathology of the cutaneous lesions revealed prominent eosinophilic infiltration with local fibrinoid change in vessel walls in the dermis and subcutis. Immunohistochemical detection of CD3, CD4, CD8 and CD40 was performed. Infiltrating eosinophils were strongly stained by anti-CD40 monoclonal antibody. One patient improved with prednisolone, pentoxifylline and nifedipine, without recurrence. The other patient initially improved with steroids, but after self-withdrawal of steroid developed digital ischaemia that evolved to severe necrosis and required amputation. Cutaneous necrotizing eosinophilic vasculitis, Raynaud's phenomenon and digital gangrene may develop as cutaneous manifestations of HES. CD40 may play a part in the pathogenesis of eosinophilic vasculitis in HES.     

Persistent hypereosinophilia with Wells syndrome

Since Wells and Smith first described cases of eosinophilic cellulitis (Wells syndrome; WS) in 1979, it has been noted that some but not all patients with WS present with eosinophilia. In the face of idiopathic persistent eosinophilia patients will also then fall within the hypereosinophilic syndrome (HES), which represents a multifarious spectrum of disorders of varying severity, causes and outcomes. In this article we propose that patients who present within the HES spectrum with cutaneous findings of WS and with no extracutaneous disease be classified as having ‘persistent hypereosinophilia with Wells syndrome’ (PHEWS).     

Skin lesions as the first manifestation of the hypereosinophilic syndrome

An unusual case of the hypereosinophilic syndrome (HES) is described in which lesions have been confined to the skin after a 2-year period of follow-up. The pathogenesis of the HES remains unsolved. A hypersensitivity phenomenon might be involved, although in this case no immunological abnormalities could be detected. The role of the eosinophilic granulocyte, however, seems to be a secondary one.     

Hypereosinophilic syndrome with various skin lesions and juvenile temporal arteritis

Hypereosinophilic syndrome (HES) is a multisystem disease with a high mortality rate. It is characterized by peripheral blood eosinophilia and eosinophilic infiltration of the skin and many other organs. The commonest cutaneous features include erythematous pruritic maculopapules and nodules, angio-oedema or urticarial plaques. However, some case reports have indicated that eosinophilic cellulitis, cutaneous necrotizing eosinophilic vasculitis, Raynaud's phenomenon and digital gangrene may also occur as cutaneous features of HES. Juvenile temporal arteritis (JTA) of unknown cause is characterized by an asymptomatic nodule in the temporal artery area in young adults. Histologically, the lesion is characterized by a significant intimal thickening with moderate eosinophilic infiltrates, constriction or occlusion of the vascular lumen and absence of giant cells. We report a patient with HES presenting with eosinophilic cellulitis, Raynaud's phenomenon, digital gangrene and JTA. JTA may also be one of the features of HES.     

Erythrodermic cutaneous T cell lymphoma with hypereosinophilic syndrome: Treatment with interferon alfa and extracorporeal photopheresis

BACKGROUND: Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders characterized by a sustained eosinophilia leading to end organ dysfunction. The lymphoproliferative variant of HES is thought to be mediated by an underlying hematologic process that drives eosinophil production through specific cytokines. Eosinophilia is also recognized as a poor prognostic factor in cutaneous T-cell lymphoma (CTCL) in which neoplastic T cells may produce eosinophilopoietic cytokines. OBJECTIVE: We report a case of HES with cardiac involvement that developed in the context of erythrodermic mycosis fungoides, discuss the possible relationship between these diseases, and speculate on the role that eosinophils might play as a prognostic factor in CTCL. METHODS: Case report and review of the literature. RESULTS: CTCL may be added to the group of lymphoproliferative disorders associated with HES. CONCLUSION: A patient with erythroderma and concomitant diagnosis of "idiopathic" HES may warrant further investigation for CTCL.     

Hydroxyethyl starch‐induced itch: Relevance of light microscopic analysis of semi‐thin sections and electron microscopy

Background: Hydroxyethyl starch (HES) is widely used as a plasma substitute for improving microcirculation. A major side effect of HES is severe pruritus caused by HES deposits in the skin. Since specific changes are difficult to see in paraffin sections, electron microscopy is the golden standard technique in the diagnosis of HES‐induced skin disease. Our aim was to compare electron microscopic search for HES deposits with other techniques. Patients and Methods: During the last ten years, we biopsied 21 patients suspected of having HES‐induced pruritus. We compared conventional microscopy with hematoxylin & eosin and toluidine blue‐stained paraffin sections, toluidine blue‐stained glycide ether‐embedded, semithin sections and transmission electron microscopy. Results: In 9 patients specific HES deposits could be found by evaluating toluidine blue stained semithin sections by light microscopy alone. In 6 of these cases electron microscopy was also done and confirmed the findings. In contrast, no specific findings due to HES deposits could be detected by conventional histology. Conclusions: If specific HES deposits are found in toluidine blue‐stained, glycide ether‐embedded semithin sections, electron microscopy is not required.     

Superficial venous thrombophlebitis as the initial manifestation of hypereosinophilic syndrome: study of the first 3 cases

BACKGROUND: Superficial venous thrombophlebitis (SVT), often perceived as benign, can coexist with hypercoagulable states. Predisposing risk factors for SVT are similar to those observed for deep venous thrombosis. Association of eosinophilia with SVT is a rare situation that can reveal neoplasia, malignant blood disorders, or vasculitis, but it has never been described in hypereosinophilic syndrome (HES). We herein describe the clinical and biological features, outcome, and response to therapy of 3 patients with SVT associated with eosinophilia that revealed HES. OBSERVATIONS: Superficial venous thrombophlebitis was the initial manifestation of HES in all 3 patients. The mean eosinophil count at diagnosis was 2.4 x 10(3)/muL. All patients received corticosteroids and anticoagulants as the initial treatment, with marked improvement of SVT and return of the eosinophil count to reference limits. All patients experienced relapse and remained dependent on corticosteroid therapy. Two patients received interferon alfa with dramatic regression of SVT, allowing a decrease in the dose of corticosteroids. CONCLUSIONS: We report, to our knowledge, the first 3 cases of SVT related to HES. Superficial venous thrombophlebitis was difficult to treat, with dependence on corticosteroid therapy and partial efficacy of anticoagulant and antiplatelet therapy. Interferon alfa was effective in preventing relapse of SVT related to HES. Mechanisms implied in this thrombogenesis are multiple and remain speculative.     

Lymphocytic variant of hypereosinophilic syndrome

Hypereosinophilia may be associated with any of several underlying diseases. Atopy or allergic drug reactions are the most common causes, but infections with bacteria and parasites should also be considered in the differential diagnosis. When thorough evaluation of a patient with chronic hypereosinophilia fails to reveal an underlying disease, the diagnosis of idiopathic hypereosinophilic syndrome (HES) should be considered. We report a patient with unexplained persistent hypereosinophilia associated with a chronic pruritic rash and an underlying diagnosis of HES (lymphocytic variant).     

皮肤Rosai-Dorfman病4例临床病理分析

目的探讨皮肤Rosai-Dorfman病(CRDD)的临床病理学特征。方法分析4例CRDD患者的临床表现,对标本进行常规病理学检查和免疫组化染色(En VisionTM)等观察。结果男2例,女2例,平均年龄50.8岁,皮损位于头面部、四肢或躯干,呈结节状、丘疹状或斑块状,其中1例为多处皮损,无合并淋巴结等其他系统病变,2例术后发生复发。光镜下病灶内见深浅不一结节状区域,浅染区见体积较大的组织细胞,呈多边形或椭圆形,其直径为淋巴细胞的10～30倍,胞质丰富,淡嗜酸性,核膜光滑,有小的嗜碱性核仁,部分组织细胞胞质内见较多淋巴细胞、浆细胞等,3例见中性粒细胞微脓肿形成,组织细胞表达S-100蛋白。结论CRDD是极少见的一种组织细胞增生性病变,其光镜图像有一定的特征性,应与慢性炎症性病变、幼年性黄色肉芽肿、纤维组织细胞瘤、Langerhans组织细胞增生症以及网状组织细胞瘤等鉴别。CRDD术后有复发可能,但预后较好。     

Immunofluorescence studies on eosinophilic granulocytes

Immunofluorescence techniques were used to find out whether immunoglobulins (Ig) and complement (C3) determinants are present on the membrane of eosinophilic granulocytes in atopic patients and in patients with an allergic contact dermatitis. Normal healthy individuals served as controls. The studies were performed with eosinophilic granulocytes in suspension and in thin cell layers. The demonstration of the presence of cytoplasmic Ig and C3 in eosinophilic granulocytes was carried out in skin specimens taken 20-30 min after injection of the antigen and in specimens taken from positive patch tests 48 h after application of the antigen. No immunoglobulins or C3 determinants could be demonstrated on the membrane of eosinophilic granulocytes in the patients or the healthy controls, when the suspension methods were used. However, in thin cell layers and in skin sections the eosinophilic granulocytes showed a positive fluorescence of the cytoplasm after having been exposed to various conjugates and a FITC solution. It is concluded that the commonly used immunofluorescence techniques tend to give non-specific staining results, most likely due to reactivity of the FITC marker of the conjugates with basic proteins present in the cytoplasm of the eosinophilic granulocyte.     

Characteristics of Japanese patients with eosinophilic fasciitis: A brief multicenter study

Eosinophilic fasciitis is a relatively rare cutaneous fibrotic condition affecting the deep fascia of the extremities, with or without peripheral blood eosinophilia. To examine the characteristics of Japanese patients with eosinophilic fasciitis, we conducted a brief, multicenter, retrospective survey at seven university hospitals. In total, 31 patients were identified as having eosinophilic fasciitis, among whom 30 patients fulfilled the Japanese diagnostic criteria. The male : female ratio was 2.3:1, and the mean age was 47.7 years. Three of the patients were under 20 years old. The possible triggering factors included muscle training, sports, walking or sitting for a long time, physical work, insect bite and drug. Co-occurrence of morphea was observed in nine cases (29%), and malignancies were associated in three (two hematological malignancies and one internal malignancy). Immunological abnormalities in the serum showed positive antinuclear antibody, positive rheumatoid factor, increased aldolase levels and increased immunoglobulin G levels. The patients were treated with either monotherapy or combination therapy by oral prednisolone (20–80 mg/day), methotrexate (6–10 mg/week), cyclosporin (100–150 mg/day), mizoribine, infliximab and phototherapy. Methylprednisolone pulse therapy was performed in six cases. By contrast, spontaneous improvement due to resting only was observed in two cases, and skin hardening was improved by withdrawal of the anticancer drug in one case. This study suggests several characteristics of Japanese patients with eosinophilic fasciitis, namely male predominance, rare pediatric occurrence, immunological abnormalities and coexistence with morphea. Systemic prednisolone is the first-line therapy, but pulse therapy is occasionally required for severe cases. The triggering events of physical stress are not so frequent as have previously been reported, and various factors or even unknown factors may be associated with the induction of eosinophilic fasciitis.     

Perineal ecthyma gangrenosum in infancy and early childhood: septicemic and nonsepticemic forms.

BACKGROUND: Ecthyma gangrenosum is characterized by necrotic ulcerations surrounded by an erythematous halo. It is secondary to Pseudomonas aeruginosa infection. Most lesions are located in the anogenital and axillary areas, but the route of infection is generally difficult to establish. OBJECTIVE: We report six children with perineal ecthyma gangrenosum and discuss predisposing factors, origin, and route of infection. METHODS: This was a retrospective clinical study. RESULTS: Three children had blood cultures positive for P. aeruginosa, and one died. Predisposing factors were present in all cases; two had received chemotherapy (neuroblastoma, acute lymphoblastic leukemia), and two had idiopathic granulocytopenia. The last two patients previously had received treatment with systemic antibiotics and had abnormal granulocyte killing several months later. CONCLUSION: Septicemic ecthyma gangrenosum can be rapidly fatal in young children and requires aggressive antibiotic therapy. Benign ecthyma gangrenosum in healthy infants may result from a modification of bowel microflora after antibiotic therapy in conjunction with maceration in the diaper area. However, careful evaluation and long-term follow-up must be done to detect neutropenia, functional abnormalities of granulocytes, or a possible immune deficiency.     

Eosinophilic folliculitis following allogeneic peripheral blood stem cell transplantation: case report and review

Eosinophilic folliculitis is considered a heterogeneous group of disorders, with several clinical subsets, sharing a common histopathological appearance. Increasing numbers of cases, following bone marrow transplantation (BMT), have been reported in recent years. We herein present a case of eosinophilic folliculitis that appeared in a 26-year-old woman 5 months after allogeneic peripheral blood stem cell transplantation as treatment for eosinophilic acute leukemia. Our review of the published cases has shown that eosinophilic folliculitis in patients after BMT could be considered as a pattern of reaction related to immune dysregulation.     

Characteristics and prognosis of idiopathic solar urticaria: a cohort of 87 cases

BACKGROUND: As little has been published on the course of idiopathic solar urticaria (SU) patients cannot receive comprehensive prognostic advice. OBJECTIVE: To determine the prognosis and photobiological characteristics of idiopathic SU. DESIGN: Historical cohort study, with inception cohort followed up from time of diagnosis. Follow-up for a median of 4 years (range, 3 months to 26 years) after diagnosis. SETTING: Tertiary referral center for the investigation of photodermatoses in Scotland. PATIENTS: The study included 87 patients, 61 (70%) of whom were female, with phototest-confirmed idiopathic SU between 1975 and 2000. Sixty patients (69%) were followed up clinically, and 25 patients (29%) were phototested on 2 or more occasions. INTERVENTIONS: Investigations at time of diagnosis included monochromator phototesting. Further monochromator phototesting was performed in those patients in whom it was clinically indicated (select subgroup), and all patients who could be traced received a follow-up questionnaire. MAIN OUTCOME MEASURES: Characteristics of SU, responsible wave bands, and prognosis for clinical resolution. RESULTS: The prevalence of idiopathic SU in Tayside, Scotland, is estimated to be 3.1 per 100 000. Action spectra were typically broad, with 63% reacting to more than 1 wave band, and the most common provoking wavelengths were the longer UV-A and the shorter visible ones. The majority of subjects were affected perennially (68%), by radiation transmitted through glass (83%) and thin clothing (76%). Coexistent polymorphic light eruption occurred in 20 patients (23%), and another photodermatosis occurred in 6 patients, 3 of whom had chronic actinic dermatitis. In those with SU alone, the mean age at onset was 41 years. The probability of clinical resolution at 5 and 10 years after diagnosis was 0.12 (95% confidence interval, 0.06-0.24) and 0.26 (95% confidence interval, 0.15-0.43), respectively. CONCLUSION: Idiopathic SU is a chronic disease. The majority of this cohort was still affected after 5 and 10 years.     

Natural course of physical and chronic urticaria and angioedema in 220 patients

BACKGROUND: Information about spontaneous remission of chronic urticaria is limited. OBJECTIVE: To investigate the natural course of urticaria, we followed up 220 adults in a prospective study. METHODS: Patients were followed up for 1 to 3 years to evaluate interventions, to detect latent causes, and to study the natural course of urticaria. The diagnosis was made by detailed history-taking as well as laboratory and provocation tests. RESULTS: Thirty-five percent of all patients were free of symptoms after 1 year. In 28.9% of patients, symptoms had decreased. Spontaneous remission occurred in 47.4% of the patients in whom no cause of their urticaria and/or angioedema could be identified and in only 16.4% of the patients with physical urticaria. A cause could be identified in 53.1% of the patients. Thirty-six percent of the patients had idiopathic urticaria. Chronic idiopathic urticaria combined with physical urticaria occurred in 10.9%. CONCLUSION: In general, the prognosis for spontaneous remission is reasonable, with the exception of the subgroup (33.2%) with physical urticaria.     

The incidence of hydroxyethyl starch-associated pruritus

BACKGROUND: Pruritus due to hydroxyethyl starch (HES) is reported with a very variable frequency but appears to be relatively uncommon in the U.K. compared with other European countries. OBJECTIVES: To determine the frequency of HES-related pruritus in patients discharged from intensive care units (ICUs) in two U.K. hospitals. METHODS: A questionnaire survey was given to 253 patients after discharge from ICU. Questions were designed to exclude pre-existing skin disease and other causes of pruritus. RESULTS: One hundred and fifty-nine completed questionnaires were suitable for analysis. Seventeen of 135 (12.6%) subjects who had received HES reported itch, as did one of 24 who had not received HES. There was no apparent relationship between the occurrence of HES-related pruritus and either the surgical indication or the brand or volume of HES infused. CONCLUSIONS: HES-related pruritus is a problem that dermatologists need to recognize; however, its frequency in the U.K., when other causes of itch are excluded, appears to be lower than suggested in some previous reported studies.     

Eosinophilic dermatoses

Morphological and functional properties of the eosinophilic granulocyte (e. G.) feature this haematopoietic stem cell-derived cell type as an important cellular component of defense mechanisms, immunologic reactions and proinflammatory/neoplastic processes. Over the last decade significant advances of the molecular pathophysiology of eosinophilic disorders enable increasingly the distinction between the more common reactive (secondary) and clonal eosinophilia including the hypereosinophilic syndrome. This review features a comprehensive clinical summary of dermatological disorders that are frequently associated with transient or persistent eosinophilia belonging to the reactive eosinophilia. The hypereosinophilic syndrome is a subset of idiopathic eosinophilia frequently associated with major tissue targets as skin, heart and others. Therefore, the hypereosinophilic syndrome has to be considered as important differential diagnosis. Most recently, the identification of selective targets (e. g. IL-5, CD52) has translated into therapeutic approaches with monoclonal antibodies such as mepolizumab, alemtuzumab or SCH55700.     

Urticarial lesions in a child with acute lymphoblastic leukemia and eosinophilia

The hypereosinophilic syndrome (HES) is defined by a longer than 6-month history of peripheral blood hypereosinophilia (greater than 1.5 x 10(9)/L), with signs and symptoms of internal organ involvement, in the absence of an identifiable cause. HES is therefore a diagnosis of exclusion. Patients have been reported who initially met the criteria for HES but subsequently developed a rare hematologic malignancy known as acute lymphoblastic leukemia with eosinophilia (ALL-Eo). We report such a case in a 10-year-old boy who presented to the pediatric dermatology clinic with unusual, urticarial skin lesions. Although skin involvement is often reported in cases of HES and ALL-Eo, such findings are variable and reports in the dermatology literature are few. We emphasize the importance of continuous monitoring for underlying malignancy in children with urticarial skin lesions in the setting of unexplained hypereosinophilia.     

Concurrent eosinophilic fasciitis and cutaneous T-cell lymphoma. Eosinophilic fasciitis as a paraneoplastic syndrome of T-cell malignant neoplasms?

Eosinophilic fasciitis has been reported to precede hematologic malignant neoplasms such as myelomonocytic leukemia, lymphocytic leukemia, and Hodgkin's lymphoma. In this case study, eosinophilic fasciitis occurred concurrently with cutaneous T-cell lymphoma (mycosis fungoides). The clinical diagnosis of eosinophilic fasciitis was based on painful sclerodermatous lesions on the extremities and trunk without acrosclerosis. There was histologic confirmation with edema and lymphocytic inflammation in the superficial muscular fascia and dermis. Deposition of immune reactants was found in the fascia and dermis. In addition, peripheral eosinophilia and circulating immune complexes were detected. The diagnosis of cutaneous T-cell lymphoma (mycosis fungoides) was based on extensive erythematous cutaneous plaques, dermal and epidermal lymphocytic atypia, loss of pan-T-cell immunologic markers, and a cutaneous lesional T-cell receptor beta-chain rearrangement by Southern blot analysis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome associated with hematologic malignant neoplasms, including mycosis fungoides. Cytokines or lymphokines released by activated immunocytes, either malignant leukocytes or normal leukocytes reacting to malignant cells, may be responsible for the eosinophilia and sclerosis seen in these associated hematologic malignant neoplasms.     

Eosinophilic Fasciitis Occurring Four Weeks after the Onset of Dialysis in a Renal Failure Patient

BACKGROUND: Eosinophilic fasciitis is a rare, scleroderma-like disease that usually affects the extremities of young to middle-aged males. The disease may cause flexion contractures and limit joint mobility and is associated with peripheral eosinophilia. The fascia, by definition, is infiltrated with mononuclear cells and typically with eosinophils. Eosinophilic fasciitis may be separated from another sclerodermatous disorder, linear scleroderma, by its response to systemic corticosteroids. The etiology is unclear but eosinophilic fasciitis has numerous disease associations. However, it has not previously been associated with renal failure and hemodialysis. OBJECTIVE: This article reports a case of eosinophilic fasciitis occurring four weeks following the onset of hemodialysis. METHODS: The clinical and histologic features confirmed the diagnosis of eosinophilic fasciitis. He was treated with systemic corticosteroids with good response. CONCLUSION: This is the first reported patient who developed eosinophilic fasciitis in close temporal relationship with the start of hemodialysis. While eosinophilic fasciitis may be coincidental with a common disorder, namely, renal failure, it is interesting to note that hemodialysis patients often have immune-regulation abnormalities and peripheral eosinophilia.