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

Abstract

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.