Rare Case of GPA/EGPA Overlap Syndrome Highlights Importance of Early Diagnosis

Early identification of granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA) overlap is critical for prognosis, long-term treatment, and management of these two distinct diseases, a case report shows.

Although few instances of this rare event have been reported, clinicians should be aware of this possibility to ensure proper and timely care for these patients.

The study, “A rare case report of polyangiitis overlap syndrome: granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis,” was published in the journal BMC Pulmonary Medicine.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a medical condition characterized by inflammation and damage of small blood vessels caused by excessive production of autoantibodies. Depending on its presentation and autoantibody pattern, the disease is divided into GPA, microscopic polyangiitis (MPA), and EGPA.

While GPA mostly affects the upper and lower respiratory tracts, as well as the kidneys, EGPA often manifests with asthma and cardiac symptoms, in addition to infiltration of immune cells, known as eosinophils, in the skin, peripheral nervous system, gastrointestinal tract, pulmonary tissues, muscles, and kidneys.

The case report describes a 50-year-old woman who was eventually diagnosed with an overlap of both GPA and EGPA, one of the few cases described in the literature.

She went to the emergency room due to an episode of coughing blood, low grade fever, night sweats, and chest discomfort. In the past, she had experienced allergic rhinitis/sinusitis and asthma, as well as recurrent upper respiratory tract infections, sinusitis, and bronchitis, approximately three times per year.

Computed tomography (CT) scans of her chest showed significant alterations, consistent with prior pulmonary symptoms and impaired respiratory function. Additional exams came back positive for Mycobacterium avium complex  infection.

She was treated with antibiotics, which significantly improved her symptoms, but four months later, the symptoms returned. At this point, chest imaging revealed a new lung tissue infiltrate and bronchiectasis, and she also had a fungal infection, which was treated with anti-fungal medicines.

A new physical evaluation revealed oral ulcers, purpuric skin lesions, and new-onset peripheral nerve damage for which she was referred for an additional opinion. Blood exams also showed an increased number of white blood cells, particularly eosinophils, as well as elevated red blood cell sedimentation rate and C-reactive protein, suggestive of active inflammation.

The patient had excess antibodies in her blood, yet she was negative for ANCA-related autoantibodies.

While her lung responsiveness was close to normal, she had mildly impaired gas exchange. A lung tissue biopsy also confirmed signs of acute and chronic inflammation with infiltration of eosinophils. Overall, the clinical findings and complex symptoms were suggestive of GPA/EGPA overlap syndrome.

“In addition to the very complex clinical picture most suggestive of EGPA/GPA overlap syndrome, … the patient also met criteria for a diagnosis of allergic bronchopulmonary aspergillosis,” the researchers reported.

“There is a possibility that the aspergillus pulmonary infection may have complicated our patient’s clinical picture,” they added.

In a literature review, the researchers found 15 other cases of EGPA/GPA overlap syndrome described between 1986 and 2017. Among them, 80% were women, all involved the lungs, 60% had sinus involvement, and more than half also had renal involvement.

“Identification of patients with polyangiitis overlap syndrome of GPA and EGPA is imperative because treatment options differ,” they wrote. While patients with EGPA may achieve disease remission with treatment with corticosteroids and anti-IL5 therapy, “patients with GPA or polyangiitis overlap syndrome may require a combination of corticosteroids, biologic therapy, and cytotoxic agents.”