Case Presentation: A 39-year-old man with relapsing remitting multiple sclerosis on ocrelizumab, last given 3 months prior to presentation, was hospitalized for one month of intermittent fevers and dry cough. He denied alcohol use but vaped both tobacco and marijuana several times daily. He had no recent travel or sick contacts. He was hospitalized recently for multifocal pneumonia, where he was treated with vancomycin, cefepime, and doxycycline and transitioned to cefpodoxime and doxycycline on discharge. After discharge, he continued to have fevers with persistent cough, chills, and diaphoresis, and therefore presented to the hospital 1 week later.On exam, he was breathing comfortably on room air, and breath sounds were diminished with bibasilar rales. Cardiac exam was unremarkable. Extremity exam showed no cyanosis or clubbing. Extensive rheumatological workup was negative. Infectious work-up, including Fungitell, acid fast bacilli blood culture, fungal blood culture, urine histoplasma antigen, Pneumocystis jiroveci smear, fungal PCR, and Cryptococcal antigen, was negative. Viral testing for cytomegalovirus and Epstein-Barr virus were negative.Repeat CT of the neck and chest with IV contrast showed worsening bilateral ground glass opacities consistent with multifocal pneumonia (Figure 1). Cultures from bronchoalveolar lavage (BAL) were negative, and there was no evidence of malignancy.Histopathology from the lung biopsy showed organizing fibroblasts within the alveolar spaces (“Masson bodies”), foci of intraalveolar fibrin, and foci suggestive of hyaline membranes, and focal intraalveolar macrophages and reactive pneumocytes were noted. He was diagnosed with ocrelizumab-induced organizing pneumonia (OP) and started on prednisone. Repeat CT of the chest 6 weeks later showed significant improvement of his organizing pneumonia with the development of left upper lobe fibrosis.
Discussion: Ocrelizumab, a recombinant anti-CD20 monoclonal antibody used in relapsing-remitting multiple sclerosis, is a potential cause of OP. When OP has an identifiable cause, it is referred to as a secondary organizing pneumonia (SOP); otherwise, it is referred to as cryptogenic organizing pneumonia (COP). OP, a form of interstitial lung disease, can clinically present as a chronic or treatment resistant pneumonia. Repeating a CT scan of the chest will often show migrating multifocal opacities compared to prior studies. Bronchoscopy is diagnostically useful only to exclude infection and eosinophilic pneumonia. Diagnosis is supported through a surgical biopsy showing characteristic polypoid plugs of organizing fibrosis called Masson bodies (Figure 2).In this patient, the biopsy findings are confounded by the patient’s vaping history. E-cigarette or vaping associated lung injury (EVALI) may have a similar clinical presentation and be virtually indistinguishable from OP histologically, with the presence of foam cells favoring the diagnosis of EVALI over OP (though foam cells are not always present). Treatment consists of a 6-12 month steroid taper and management or elimination of the underlying cause. Prognosis in these patients is good, however, some patients may develop some degree of pulmonary fibrosis.
Conclusions: Secondary organizing pneumonia is a rare side effect of ocrelizumab but is increasingly reported. There is a substantial histologic overlap between COP, ocrelizumab-induced SOP, and EVALI. Clinical context is key to supporting one diagnosis over the other.
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