Intravascular Nematodes Mimicking GPA Michael 1Donald
1 Varrone ,
Douglas
2 Anderson ,
and Barbara Zucker School of Medicine at Hofstra/Northwell
2Department
and Brian
2 Fallon
of Cardiothoracic Surgery at Northwell Health
Background
Clinical Summary
Discussion
Granulomatosis with polyangiitis (GPA) also known as Wegener’s granulomatosis, is a rare type of antineutrophil cytoplasm antibody (ANCA) associated 1 vasculitis . A hallmark of GPA is granulomatous inflammation and small to medium size vessel 2 vasculitis . In the United States, the estimated prevalence is 3.0 per 100,000 population2, and typically arises from unknown causes3. There is a strong link between infections and development of GPA, but an exact mechanism by which this occurs 4,5 is unknown . The first case of a parasite causing 6 GPA was reported in 1995 . However, parasitic infections are a rare cause of GPA. More commonly, 7 parasitic infections cause eosinophilic meningitis . Angiostrongyliasis is a parasitic nematode that 7 typically does not mimic GPA . It is important for physicians to be aware of this potential rare etiology of GPA, so that effective treatment can be appropriately provided.
A 59-year-old man with a history of diabetes mellitus, hypertension, hyperlipidemia, fibromyalgia, and rheumatoid arthritis presented to the emergency department with body aches, fever, chills, and weakness for one week. Three weeks prior, he had similar symptoms while in Guatemala, where he was evaluated at a hospital and diagnosed with Dengue virus. He was admitted following his current presentation and found on CT scan to have bilateral pulmonary peripheral opacities. Without a clear diagnosis, he was started on empiric azithromycin and ceftriaxone for pneumonia and albuterol/ipratropium for interstitial lung disease. He underwent a lab-based evaluation for parasitic and tuberculosis infection, which was negative. After one week of initial treatment, a repeat CT scan demonstrated an increase in size of the opacities. Due to the worsening findings on CT and unclear etiology of these opacities, a video assisted thoracoscopic surgery (VATS) wedge biopsy was performed. Preliminary results suggested pulmonary angiitis, consistent with GPA in the right lower lobe and right middle lobe. The patient was then treated with prednisone to treat the suspected GPA and piperacillin/tazobactam to treat the underlying infection until discharge on post-operative day #7. After the patient was discharged, intravascular nematodes were identified, associated with eosinophilic vasculitis, eosinophilic pneumonia, and foci of organizing pneumonia in the background of emphysematous changes (Figures 1, 2, and 3). Special stains for fungi and bacilli were negative. Potential differential diagnoses included dirofillaria sp. and angiostongylus sp. The Centers for Disease Control (CDC) was consulted, and classification is still pending.
The two nematodes species suspected in this patient’s infections are Dirofillaria sp. and Angiostongylus sp.. Angiostrongylus sp. is a rat lungworm8. Angiostrongylus sp. is the most common cause of eosinophilic meningitis worldwide9. Typical symptoms of infection are headache, neck stiffness, paresthesias, and vomiting8. It is rare to find Dirofillaria localized to the lungs, and when encountered there, patients are usually asymptomatic10,11. The infection is often discovered incidentally and mistaken for primary or metastatic lung tumors10. Only 2,827 cases of human angiostrongyliasis have been documented worldwide as of 20088. Infection often leads to eosinophilic meningitis7. It is extremely rare to find angiostrongyliasis causing pulmonary angiitis, with only the third case ever reported in 20207. Human dirofilariasis and angiostrongyliasis are rare but must be included in the differential diagnosis of patients with pulmonary nodules8,10,11,12. Patients are typically mistaken to have a lung tumor, which leads to unnecessary surgery only to discover an infection10. Alternatively, these patients can be diagnosed using imaging in combination with serological tests and discovery of peripheral blood eosinophilia13. Our case represents a rare occurrence of a parasitic infection mimicking vasculitis. It is critical for physicians to differentiate the two, as treatment plans are significantly different. The recommended treatment for GPA is cyclophosphamide plus corticosteroids, while the treatment for most parasitebased vasculitis involves an anthelminthic regimen7,14. This difference in treatment makes it crucial to cease immunosuppressive therapies for vasculitis and replace them with the correct anthelminthic program7. In our case, the parasitic infection mimicked GPA under the preliminary biopsy reports, although our patient was negative for c-ANCA antibodies. The diagnosis of the parasitic infection causing an eosinophilic vasculitis was made too late to alter the hospital treatment.
Figures
Resources 1Lutalo,
Figure 1. Cross section through a small vessel in the lungs containing nematodes associated with vasculitis.
Figure 2. Cross section through a small vessel in the lungs containing nematodes associated with vasculitis.
Figure 3. Cross section through a small vessel in the lungs containing nematodes associated with vasculitis.
P. M., & D'Cruz, D. P. (2014). Diagnosis and classification of granulomatosis with polyangiitis (aka Wegener's granulomatosis). Journal of autoimmunity, 48, 94-98. 2Cotch, M. F., Hoffman, G. S., Yerg, D. E., Kaufman, G. I., Targonski, P., & Kaslow, R. A. (1996). The epidemiology of Wegener's granulomatosis. Estimates of the five‐year period prevalence, annual mortality, and geographic disease distribution from population‐based data sources. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, 39(1), 87-92. 3Gross, W. L., Trabandt, A., & Csernok, E. (1998, September). Pathogenesis of Wegener's granulomatosis. In Annales de Medecine Interne (Vol. 149, No. 5, pp. 280-286). 4George, J., Levy, Y., Kallenberg, C. G., & Shoenfeld, Y. (1997). Infections and Wegener's granulomatosis--a cause and effect relationship?. QJM: monthly journal of the Association of Physicians, 90(5), 367-373. 5Tadema, H., Heeringa, P., & Kallenberg, C. G. (2011). Bacterial infections in Wegener's granulomatosis: mechanisms potentially involved in autoimmune pathogenesis. Current opinion in rheumatology, 23(4), 366-371. 6Pirisi, M., Gutiérrez, Y., Minini, C., Dolcet, F., Beltrami, C. A., Pizzolito, S., Piztus, E., & Bartoli, E. (1995). Fatal human pulmonary infection caused by an Angiostrongylus-like nematode. Clinical infectious diseases, 20(1), 59-65. 7Elghawy, A. A., Skopis, M., Davis, J., & BagOzbek, A. (2020). Angiostrongyliasis infection masquerading as granulomatosis with polyangiitis: a casebased review. RHEUMATOLOGY INTERNATIONAL. 8Wang, Q. P., Lai, D. H., Zhu, X. Q., Chen, X. G., & Lun, Z. R. (2008). Human angiostrongyliasis. The Lancet Infectious Diseases, 8(10), 621-630. 9Lindo, J. F., Escoffery, C. T., Reid, B., Codrington, G., Cunningham-Myrie, C., & Eberhard, M. L. (2004). Fatal autochthonous eosinophilic meningitis in a Jamaican child caused by Angiostrongylus cantonensis. The American journal of tropical medicine and hygiene, 70(4), 425-428. 10Abdel-Rahman, S. M., Mahmoud, A. E., Galal, L. A. A., Gustinelli, A., & Pampiglione, A. S. (2008). Three new cases of human infection with Dirofilaria repens, one pulmonary and two subcutaneous, in the Egyptian governorate of Assiut. Annals of Tropical Medicine & Parasitology, 102(6), 499-507. 11Echeverri, A., Long, R. F., Check, W., & Burnett, C. M. (1999). Pulmonary dirofilariasis. The Annals of thoracic surgery, 67(1), 201-202. 12Cui Y, Shen M, Meng S. Lung CT findings of angiostrongyliasis cantonensis caused by Angiostrongylus cantonensis. Clin Imaging. 2011;35(3):180183.doi:10.1016/j.clinimag.2010.05.004 13Kunst, H., Mack, D., Kon, O. M., Banerjee, A. K., Chiodini, P., & Grant, A. (2011). Parasitic infections of the lung: a guide for the respiratory physician. Thorax, 66(6), 528-536. 14Almouhawis HA, Leao JC, Fedele S, Porter SR. (2013). Wegener's granulomatosis: a review of clinical features and an update in diagnosis and treatment. J Oral Pathol Med. 2013;42(7):507-516. doi:10.1111/jop.12030