In a large retrospective study recently published by the French Vasculitis Study Group to better define the real-world EGPA experience, the clinical characteristics of 383 patients with EGPA were described.3 Interestingly, only 31% were ANCA positive, and those that were ANCA negative had lower BVAS scores than those who were ANCA positive (18.4 vs. 20.7), with less frequent renal disease, peripheral neuropathy and otolaryngeal disease. Anecdotally, pulmonologists frequently encounter a population of patients with features strongly suggestive of EGPA that is characterized by ANCA negativity, prominent sinus and lower respiratory features, including severe asthma symptoms, and pulmonary infiltrates, in the setting of high-grade peripheral eosinophilia—and importantly, no evidence of vasculitis.
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Explore This IssueJune 2015
The dichotomies that exist under the umbrella of EGPA—ANCA positive vs. ANCA negative, respiratory predominant symptoms vs. systemic symptoms, vasculitic vs. nonvasculitic—may ultimately prove to have implications for treatment. However, corticosteroids remain the mainstay of therapy, and chronic low-dose steroids can often control disease activity in ANCA-negative patients with predominant respiratory manifestations. In patients with greater systemic manifestations and suspected active vasculitis that may be more commonly seen in rheumatology practices, a greater degree of immunosuppression (e.g., cyclophosphamide, azathioprine, mycophenolate mofetil) is often required for both induction and maintenance therapy—similar to approaches for other forms of systemic vasculitis. Mepolizumab (GlaxoSmithKline) and Reslizumab (Teva), monoclonal antibodies directed against interleukin 5 (IL-5, i.e., a cytokine that has a key central role in the differentiation, survival and migration of eosinophils), are investigational agents that specifically target eosinophils and represent promising novel therapeutic options for EGPA of all phenotypes.
In open-label pilot studies, blocking IL-5 with mepolizumab has been observed to allow for reduction in corticosteroid dosage with EGPA.4 Mepolizumab is currently being studied in a placebo-controlled, double-blind trial in patients with refractory or relapsing EGPA (clinicaltrials.gov identifier: NCT02020889).
Diffuse Fasciitis with Eosinophilia
Another eosinophilic disorder that may present to the rheumatologist is diffuse fasciitis with eosinophilia (DFE), also called eosinophilic fasciitis or Shulman’s syndrome, an idiopathic disease classically characterized by woody induration of the skin and peripheral and tissue eosinophilia.5,6 Although the etiology of this disease is not known, in some cases, a history of recent, severe exertion has been associated with its development. A hallmark of DFE is extensive skin thickening, and it is important to distinguish this condition from that of systemic scleroderma (SSc).5,7
The clinical features of DFE include severely indurated and thickened skin, typically symmetric in nature and involving the proximal extremities. Truncal involvement is common. Autoantibody negativity and the presence of peripheral eosinophilia distinguish DFE from SSc. Similarly, the distal extremities and face are typically spared, and importantly, there is an absence of Raynaud’s phenomenon or other internal organ manifestations characteristic of SSc.5,7 This proximal skin involvement—with sparing of distal extremities—is one of the critical clues to differentiating DFE from SSc.5,7 The woody induration may give a characteristic peau d’orange appearance. The severe fibrosis of the fascia can result in limitations in range of motion and permanent flexion contractures of the involved extremities.