Via Research Recognition Day 2024 VCOM-Carolinas

Clinical Case-Based Reports

A CASE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGITIS IN A MIDDLE-AGED MAN WITH NEUROCOGNITIVE SYMPTOMS Caitlin Biderman, OMS III, Marc Ciesco, DO Bon Secours St. Francis, Greenville, SC

Abstract

Case Presentation

Conclusions/Context/Impact

The patient described in the case below is a 64-year-old male that presented with a several day history of lower extremity purpura and blistering. He has a past medical history of myeloperoxidase anti-neutrophilic cytoplasmic antibody (MPO-ANCA) vasculitis and had been started on steroids a few days prior to admission. Other medical history includes moderate persistent asthma, dementia with expressive aphasia, chronic congestive heart failure with an implantable cardioverter-defibrillator, atrial fibrillation, hypertension, gastroesophageal reflux disease, and Raynaud’s phenomenon. Lab workup demonstrated elevated troponin, leukocytosis, and eosinophilia. Hematology/oncology was consulted, and a skin biopsy and bone marrow biopsy were completed. Pathology was consistent with a diagnosis of Eosinophilic Granulomatosis with Polyangiitis (EGPA). A CT without contrast indicated that paranasal sinus disease was present, which coincides with a diagnosis of EGPA. He was started on prednisone, and he had a clinical improvement in his asthma symptoms, his purpura, his blistering, his eosinophilia, and his expressive aphasia. He was discharged and followed with his pulmonologist, his neurologist, his rheumatologist, his wound care specialist, and his hematologist/oncologist. He has been continuing medications as listed in table 2. A continued improvement has been seen in his symptoms and he will start rituximab soon. EGPA is a multi-organ disease that affects small and medium sized vessels. EGPA most often presents in patients with a history of asthma, allergic rhinitis, and sinusitis. EGPA affects the lungs, heart, and gastrointestinal system. In later stages, patients present with purpura, polyneuropathy, and renal involvement. EGPA patients can be classified as MPO-ANCA positive or MPO-ANCA negative and, depending on this classification, presentations may vary. Standard treatment to induce remission and limit relapses is systemic glucocorticoids. For patients with more severe disease, cyclophosphamide, rituximab, or other biologics are added. This patient’s disease is a rare condition, a nd it is important that EGPA cases be studied and documented more to add to the growing body of literature and understanding of the disease. Furthermore, he presented with a history of dementia with expressive aphasia. In the literature, few cases of EGPA with central nervous system involvement causing memory issues have been documented. Per his neurologist his memory is impaired, but it has significantly improved since undergoing treatment for EGPA. It is unknown how much his underlying dementia can be contributed solely to his EGPA diagnosis. Nevertheless, his clinical presentation and therapeutic regimen are essential for monitoring the severity of his neurologic symptoms and how EGPA may be linked to the development of dementia. • Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease, with an annual incidence and prevalence of 1 to 3 per 1,000,000 and 11 to 45 per 1,000,000 with no gender predominance, that primarily affects small and medium sized vessels. 1 Histology illustrates granulomatous inflammation and necrotizing vasculitis. The disease was first described in 1951 by J. Churg and L. Strauss after studies on autopsies of thirteen patients with asthma, eosinophilia, and organ lesions such as cardiac insufficiency, renal failure, and neuropathy. • EGPA progresses in three phases usually. First is the prodromal phase, where patients present with asthma and allergic rhinosinusitis. The eosinophilic phase presents next, where patients present with pulmonary infiltrates, eosinophilic cardiomyopathy, and/or gastrointestinal involvement. The vasculitic phase presents last, where the nervous system, skin, and kidneys are affected. In this phase, patients present with neuropathy, purpura, and less commonly, renal failure. 2 Patients often present with cutaneous lesions and then a diagnosis of EGPA is often made based on patient history, lab work, and imaging. • EGPA is classified as myeloperoxidase anti-neutrophilic cytoplasmic antibody (MPO-ANCA) positive or negative. Patients that are MPO-ANCA positive more often present with vasculitis symptoms, including palpable purpura, peripheral neuropathy, rapidly progressive glomerulonephritis, alveolar hemorrhage, and an increased tendency to relapse. Patients that are MPO-ANCA negative more often present with eosinophilic-driven symptoms, including lung infiltrates, myocardiopathy, and gastrointestinal issues, as well as higher mortality. 3 • Although nervous system involvement in the form of peripheral mononeuropathy is a common presentation associated with EGPA, central nervous system involvement is less common. Review of literature reports that central nervous system involvement in EGPA has been reported in 5.2% and 8.7% of EGPA patients, primarily in the form of cerebral infarcts and subarachnoid hemorrhages. 4 Introduction

• In the case reported, the patient presented with worsening purpura and blistering and upon workup, was found to have high levels of eosinophils. • A diagnosis of EGPA was made after skin biopsy and he was given the standard monotherapy treatment for EGPA, high-dose systemic corticosteroids. Immunosuppressive agents, such as cyclophosphamide, methotrexate, azathioprine, mofetil, mycophenolate, or rituximab are often added to corticosteroid treatment, depending on the degree of organ involvement. 5 The patient is scheduled to start rituximab after the wounds from the purpura heal. • The patient in the case reported is ANCA positive and has already seen improvement with prednisone treatment in majority of his symptoms, including his dementia symptoms. Aphasia and memory issues still persist; however, an overall improvement has been seen. • It is unclear if his dementia is directly linked to the EGPA or a separate etiology that happened to improve upon prednisone treatment. Being an MPO-ANCA positive patient, it is possible based upon literature that there is a link. Additionally, both the patient’s cutaneous symptoms and his worsening cognitive dysfunction during periods of sickness are suggestive of a flare up of EGPA and an association of EGPA and the dementia. • However, further studies are needed to assess the association between EGPA and dementia. The patient has an overall good prognosis at this time and is being closely monitored by his treatment team for changes in his condition and flare-ups of EGPA. It is unknown at this time how he will respond to the rituximab and what his long-term care will look like. • His case adds to the growing literature on the rare disease of EGPA and may possibly aid the community in studying the varying presentations of EGPA and the degree to which it may be associated with dementia.

• 64-year-old Caucasian male presented to the emergency department with worsening purpura and blistering of both legs that had been progressing over the preceding days (Figure 1). He had similar lesions on his hands that had improved prior to presentation (Figure 2). • The patient first started having asthma symptoms in his 20s and he has had longstanding issues with his lungs and nostrils, such as ulcerated areas. He has a 10 – 15-year history of dementia that started with aphasia and progressed to include other cognitive domains. His altered mentation waxes and wanes during the day and is worse in the mornings and evenings. Per his family, certain medications and periods of sickness have worsened his condition. During such periods of sickness and worsened altered mentation, he has also experienced a rash breaking out. He does have periodic visual hallucinations. His symptoms have been stable for the last 6 years. • On physical exam, the patient was alert and reactive, but slow at comprehension and difficulty with word finding. Per his family, this was close to his baseline, and he has a 10 – 15-year history of dementia symptoms. Other physical exam findings include bilateral leg pain. • Labs demonstrated leukocytosis, eosinophilia, anemia, elevated brain natriuretic peptide and elevated troponin. CT without contrast demonstrated no evidence of acute intracranial abnormality and indicated that paranasal sinus disease is present. • The patient was referred to hematology/oncology and a skin biopsy was completed, which was consistent with EGPA (Figure 3). • A bone marrow biopsy was completed as well, which indicated variable marrow cellularity and overall 40% trilineage hematopoietic maturation and eosinophilia. • Flow cytometric analysis showed relative eosinophilia, fluorescence in situ hybridization was normal, karyotype was normal, and peripheral blood smear illustrated normochromic normocytic anemia. Cytogenetics demonstrated no pathologic mutations or detected genes. • The patient was started on high-dose prednisone and, shortly thereafter, his leukocytosis, purpura, blistering, rash, and mentation and expressive aphasia all began to improve. Other medications that he received throughout hospital course include those outlined in table 1. He was discharged after 5 days and medications include those outlined in table 2. • Since being discharged, the patient has had follow-up appointments with his neurologist, his pulmonologist, his hematologist, and his wound care specialist. He was started on Santyl to try to remove necrotic tissue and protein supplementation of 100 mg a day to support cell rejuvenation. Since starting treatment with systemic corticosteroids, his various clinical symptoms have markedly improved. At the time of writing, he is on sulfamethoxazole/trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis and is due to begin rituximab soon for chronic immunosuppressive therapy. • Per his family, he will begin rituximab as soon as his wounds are healed. He is still presenting with bilateral neuropathic leg pain, shuffling gait, red hands, memory issues, and aphasia. He will continue to be followed and monitored.

Figure 3. Histology slides, illustrating necrotizing granulomatous inflammation and eosinophilic infiltration. These histological features confirm the diagnosis.

References

1. Springer JM, Kalot MA, Husainat NM, et al. Eosinophilic Granulomatosis with Polyangiitis: A Systematic Review and Meta Analysis of Test Accuracy and Benefits and Harms of Common Treatments. ACR Open Rheumatol . 2021;3(2):101-110. doi:10.1002/acr2.11194 2. Fijolek J, Radzikowska E. Eosinophilic granulomatosis with polyangiitis - Advances in pathogenesis, diagnosis, and treatment. Front Med (Lausanne) . 2023;10:1145257. Published 2023 May 3. doi:10.3389/fmed.2023.1145257 3. Vega Villanueva KL, Espinoza LR. Eosinophilic Vasculitis. Current Rheumatology Reports . 2020;22(1). doi:https://doi.org/10.1007/s11926-020-0881-2 4. Xu D, Xu H, Wang F, et al. Multiple Distinctive Demyelinating Lesions Caused by Eosinophilic Granulomatosis With Polyangiitis: Case Report and Literature Review. Frontiers in Neurology . Published online March 11, 2019. doi:https://doi.org/10.3389/fneur.2019.00213 5. Mullin EW, Vasileia Aristotelidou, Blackburn D, Jenkins TM, Marios Hadjivassiliou. Cognitive deficits in vasculitis of the nervous system: a cross-sectional study. Postgraduate Medicine . Published online September 11, 2019. doi:https://doi.org/10.1080/00325481.2019.1664256

We would like to acknowledge Bon Secours St. Francis. We also would like to acknowledge the patient’s family for allowing us to participate in the care of their loved one and present the case.

Table 2. Patient’s discharge medication regimen

Table 1 . Patient’s medications throughout hospital course

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