Cutaneous Eosinophilic Vasculitis Research Articles

Development of ANCA-Negative Eosinophilic Granulomatosis With Polyangiitis 19 years After Onset of Eosinophilic Pustular Folliculitis.

To the Editor: A 47-year-old Japanese man visited our department, complaining of itchy erythema on the bilateral cheeks. Physical examination showed symmetrical infiltrative erythematous plaques with small papules and tiny pustules at the periphery, as well as papular lesions under the nostrils and around the lips (Fig. 1A). Biopsy revealed infiltration of neutrophils and eosinophils in the sebaceous glands (Fig. 1B). The patient was diagnosed as having eosinophilic pustular folliculitis (EPF), and oral intake of indomethacin (200 mg/d) resulted in a favorable effect. At the age of 56 years, he developed bronchial asthma, and a few years later, he complained of numbness of the bilateral lower legs, which was diagnosed as neuropathy. Nineteen years after the initial visit to us, he was referred to us for skin lesions. Physical examination showed brownish infiltrative plaques, papules, and vesicles on the lower extremities (Fig. 1C). Laboratory examination showed an elevated eosinophil rate in the peripheral blood (14%), and serum IgE was elevated (213 IU/mL; normal <170). Neither proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibody (ANCA) nor myeloperoxidase (MPO)-ANCA was detected in the serum. HIV was negative. Histopathological examination revealed prominent infiltration of eosinophils in and around the sebaceous glands and vessels in the mid dermis (Fig. 1D). Higher magnification revealed a number of eosinophil infiltration in the vessel walls with degranulation of the infiltrated eosinophils and alteration of the affected pale-stained vessel walls, loss of endothelial cells of the affected venous vessel in the mid dermis (Fig. 1E), consistent with eosinophilic vasculitis. Neither fibrinoid degeneration of the vessel walls nor neutrophil infiltration with nuclear dust was observed. Extravascular giant cells were scattered in the dermis (Fig. 1F). Elastica van Gieson staining revealed that the affected vessels were venules. Renal disease was not observed. The patient was treated with inhaled corticosteroid for bronchial asthma, and his skin lesions were treated with topical corticosteroid ointment.FIGURE 1.: A, Facial infiltrative erythematous plaques with small papules and tiny pustules at the periphery. B, Biopsy specimen taken from the cheek showed marked infiltration of neutrophils and eosinophils in the sebaceous glands. C, Brownish infiltrative plaques, papules, and vesicles on the lower extremities. D, Histopathological features showing dermal infiltration of a number of eosinophils in and around the sebaceous glands and vessels in the mid dermis. E, Higher magnification reveals prominent infiltration of eosinophils in and around the vessel walls with eosinophilic degranulation (arrows), alteration of the affected vessel walls, and loss of endothelial cells (encircled by dotted square). F, Extravascular giant cells in the dermis. H–E, stain, original magnification: B; ×200, d; ×100, e; ×400, f; ×400).Eosinophilic pustular folliculitis is a sterile inflammatory dermatosis, frequently involving the face, presenting with annular erythematous plaques with superficial papulopustules at the periphery.1 Eosinophilic pustular folliculitis is histopathologically associated with folliculotropic infiltration of eosinophils. Our case was diagnosed as classic EPF and successfully treated with indomethacin. Thereafter, EPF did not recur, but the patient developed eosinophilic granulomatosis with polyangiitis (EGPA) 19 years later. Eosinophils play a crucial role in the pathogenesis of EGPA and release of mediators, that is, major basic protein, eosinophilic cationic protein, eosinophil peroxidase, and eosinophil-derived neurotoxin, as well as various cytokines by degranulation is important in the development of eosinophilic vasculitis.2 In EGPA, cutaneous eosinophilic vasculitis is rarely seen. The inflammatory process of eosinophilic vasculitis in EGPA begins as an angiocentric infiltrate of eosinophils in and around the small vessels.3 In the present case, angiocentric infiltrates of inflammatory cells in the affected vessels' wall were almost exclusively eosinophils without either neutrophils or histiocytes. The affected vessels were venules, and the arteries were intact. These findings suggest that the present case is the initial stage of EGPA with eosinophilic vasculitis. In addition, the present case was ANCA negative and renal involvement was absent. Previous studies have suggested that MPO-ANCA–positive patients frequently develop neutrophilic vasculitis with renal involvement, while those with eosinophil-predominant eosinophilic vasculitis frequently revealed serological ANCA negative and developed lung infiltrates, myocardiopathy, and gastrointestinal manifestations but the absence of renal involvement.4,5 Further studies are necessary to investigate the associations of cutaneous manifestations, eosinophilic vasculitis, and ANCA. Histopathological features of hypereosinophilic syndrome are eosinophilic spongiosis in the epidermis, superficial and deep dermal perivascular and interstitial infiltrate of numerous eosinophils and lymphocytes6; however, neither vasculitis nor histiocytic giant cells are observed. Therefore, hypereosinophilic syndrome was excluded in the present case. To the best of our knowledge, this is the first report of concurrent EPF and EGPA. Because EGPA occurred nearly 20 years later, the coexistence may be incidental. Nevertheless, eosinophil activation may have played a role in the induction of both disorders in our patient.

Recurrent cutaneous eosinophilic vasculitis characterized by annular purpuric lesions: A case report

A 71-year-old woman presented with a persistent, intensely pruritic cutaneous eruption localized on the palmoplantar regions, lips and palate. The histological findings allowed to make the diagnosis of recurrent cutaneous eosinophilic vasculitis, a very rare cutaneous vasculitis characterized clinically by multiple erythematous or purpuric erythematous papules or plaques or angioedema with a relapsing course in the absence of systemic involvement and histologically by a necrotizing vasculitis of the dermal small vessels with a dominant eosinophilic infiltration. The patient was treated with oral methylprednisolone and pentoxifylline which led to a rapid resolution of the cutaneous lesions.

Recurrent Cutaneous Eosinophilic Vasculitis: A Rare Entity.

Recurrent cutaneous necrotizing eosinophilic vasculitis is a rare entity described by Chen et al. It has a benign course without any systemic involvement. However, often long-term treatment with systemic steroids is required. The exact etiopathogenesis remains unknown. We report a female patient, who presented with recurrent pruritic purpuric papules and plaques affecting different body parts of long duration. Disease was well controlled with low dose systemic steroids, but invariably recurred on its withdrawal. Histology revealed the features of eosinophilic vasculitis. Subsequent detailed evaluation ruled out systemic involvement, underlying diseases, and any precipitating factors. Hence, a diagnosis of recurrent cutaneous eosinophilic vasculitis was made. Patient showed excellent response to prednisolone, and on tapering the drug, it was found that she needed a maintenance dose of 5 mg/day. We did not come across any previous reports of recurrent cutaneous eosinophilic vasculitis from India.

Eosinophilic Skin Diseases: A Comprehensive Review.

Eosinophilic skin diseases, commonly termed as eosinophilic dermatoses, refer to a broad spectrum of skin diseases characterized by eosinophil infiltration and/or degranulation in skin lesions, with or without blood eosinophilia. The majority of eosinophilic dermatoses lie in the allergy-related group, including allergic drug eruption, urticaria, allergic contact dermatitis, atopic dermatitis, and eczema. Parasitic infestations, arthropod bites, and autoimmune blistering skin diseases such as bullous pemphigoid, are also common. Besides these, there are several rare types of eosinophilic dermatoses with unknown origin, in which eosinophil infiltration is a central component and affects specific tissue layers or adnexal structures of the skin, such as the dermis, subcutaneous fat, fascia, follicles, and cutaneous vessels. Some typical examples are eosinophilic cellulitis, granuloma faciale, eosinophilic pustular folliculitis, recurrent cutaneous eosinophilic vasculitis, and eosinophilic fasciitis. Although tissue eosinophilia is a common feature shared by these disorders, their clinical and pathological properties differ dramatically. Among these rare entities, eosinophilic pustular folliculitis may be associated with human immunodeficiency virus (HIV) infection or malignancies, and some other diseases, like eosinophilic fasciitis and eosinophilic cellulitis, may be associated with an underlying hematological disorder, while others are considered idiopathic. However, for most of these rare eosinophilic dermatoses, the causes and the pathogenic mechanisms remain largely unknown, and systemic, high-quality clinical investigations are needed for advances in better strategies for clinical diagnosis and treatment. Here, we present a comprehensive review on the etiology, pathogenesis, clinical features, and management of these rare entities, with an emphasis on recent advances and current consensus.

Churg-Strauss syndrome: Report of 3 cases

Churg-Strauss syndrome (CSS) is a vasculitis of medium to small sized vessels. Diagnosis is mainly clinical with fi ndings of asthma, eosinophilia, rhinosinusitis and signs of vasculitis in major organs. This is a rare syndrome of unknown etiology, affecting both genders and all age groups. Outcome and long-term survival are usually good with steroids alone or in combination with immunosuppressive agents. The syndrome has a low mortality rate compared with other systemic vasculitides. We report three patients with CSS from Ardabil, who presented with asthma, pansinusitis, peripheral eosinophilia, peripheral neuropathy, cutaneous eosinophilic vasculitis. The diagnosis of CSS was made by the diagnostic criteria of American College of Rheumatology (ACR). CSS is typically suspected in patients whose asthma is poorly controlled on moderate doses of inhaled glucocorticoids. Prolonged treatment of asthma with glucocorticoid therapy may partially or totally suppress the usual clinical signs of untreated CSS. The disease may therefore not become evident until glucocorticoids are reduced or stopped.

Successful Treatment with Tacrolimus in a Case of the Glucocorticoid-Dependent Recurrent Cutaneous Eosinophilic Vasculitis

Successful Treatment with Tacrolimus in a Case of the Glucocorticoid-Dependent Recurrent Cutaneous Eosinophilic Vasculitis

Chronic Periaortitis (Retroperitoneal Fibrosis) Concurrent with Recurrent Cutaneous Eosinophilic Vasculitis

Chronic periaortitis (CP) is usually accompanied by at least mild manifestations of systemic autoimmunity; however, skin manifestations are rare. Here, we report an 82-year-old woman presenting with a pruritic annular eosinophilic dermatosis that led to the diagnosis of recurrent cutaneous eosinophilic vasculitis (RCEV) coexisting with a latent CP. The present paper is reminder that a CP should be included as a potential differential diagnosis in the elaboration of patients with cutaneous vasculitis that is suspicious of underlying autoimmunity.

Establishment of Experimental Eosinophilic Vasculitis by IgE-Mediated Cutaneous Reverse Passive Arthus Reaction

Prominent eosinophil infiltration is a characteristic of some forms of vasculitis, such as Churg-Strauss syndrome, also known as allergic granulomatous vasculitis. In the current study, we established a mouse model of cutaneous eosinophilic vasculitis by the cutaneous reverse passive Arthus reaction using IgE injection instead of IgG. Wild-type C57BL/6 mice were injected with IgE anti-trinitrophenyl antibodies, followed immediately by intravenous administration of trinitrophenyl bovine serum albumin. IgE-mediated immune complex challenge induced substantial hemorrhage with marked infiltration of eosinophils in which neutrophils, mast cells, and macrophages were also mixed. This finding contrasted remarkably with the neutrophil-dominant infiltration pattern in IgG-mediated immune complex challenge. In the lesion, the expression level of monocyte chemotactic protein-3 was increased, and anti-monocyte chemotactic protein-3 treatment resulted in a significant but incomplete blockade of eosinophil recruitment. Furthermore, mice lacking E-selectin, P-selectin, L-selectin, or intercellular adhesion molecule-1, as well as wild-type mice that received anti-vascular cell adhesion molecule-1-blocking antibodies were assessed for the IgE-mediated Arthus reaction. After 24 hours, the loss of P-selectin resulted in a significant reduction in eosinophil accumulation compared with both wild-type mice and other mouse mutants. Collectively, the Fc class of immunoglobulins, which forms these immune complexes, critically determines the disease manifestation of vasculitis. The IgE-mediated cutaneous reverse passive Arthus reaction may serve as an experimental model for cutaneous eosinophilic infiltration in vasculitis as well as in other diseases.

Recurrent cutaneous eosinophilic vasculitis presenting as annular urticarial plaques.

Sir, Clinical and histological cutaneous necrotizing vasculitis of dermal small vessels with an almost exclusively eosinophilic infiltration and without any features of the systemic disease has recently been described by Chen et al. as recurrent cutaneous eosinophilic vasculitis (RCEV) (1, 2). This disease is rare and only a few cases have been reported (1–4). We here describe one more case of RCEV presenting as annular urticarial plaques.

Eosinophilic vasculitis syndrome: Recurrent cutaneous eosinophilic necrotizing vasculitis

We recently identified a syndrome of recurrent cutaneous eosinophilic vasculitis in three patients. These patients had in common widespread pruritic, erythematous, purpuric papules and angioedema of face and hands associated with peripheral blood eosinophilia. Eight skin biopsies from these three patients all showed necrotizing vasculitis of the small vessels of the skin, with exclusively eosinophilic infiltration and minimal or no leukocytoclasis. The disease followed a chronic course, with recurrent, itchy, swelling skin lesions and without evidence of systemic involvement over observation periods of 3, 17, and 23 years. The skin lesions responded promptly to systemic steroid treatment, but two patients required maintenance doses for control of the disease. Immunofluorescence studies showed marked deposition of the cytotoxic eosinophil granule major basic protein in the affected vessel walls. Eosinophil-active cytokine IL-5 was detected in the serum of one patient. Expression of the vascular cell adhesion molecule-1 for eosinophil adherence was detected on the endothelium of the affected vessels. Because this disease showed distinctive clinical manifestations and characteristic histopathological features, we believe it is a distinct entity and should be distinguished from other types of vasculitis.