Hussein, S.

Abstract Introduction:IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition marked by lymphoplasmacytic infiltrates that tend to affect various organs, leading to diverse clinical manifestations. While commonly linked to conditions like pancreatitis and sialadenitis, it can also impact the lungs, causing pulmonary masses, consolidations, or pneumonia. Key histopathological features include IgG4-positive plasma cells and storiform fibrosis, although these may not always be present. Case Presentation: We present a case of an 82-year-old male with a past medical history significant for pulmonary cryptococcal infection and a previous COVID-19 infection, who presented to our pulmonology clinic with fatigue for two months followed by an upper respiratory infection that did not respond to several rounds of antibiotics. A chest CT scan revealed bilateral consolidative airspace opacities and lymphadenopathy. Subsequent bronchoscopy with transbronchial biopsy and bronchoalveolar lavage (BAL) suggested a possible cryptococcal infection; however, his symptoms did not improve after a course of fluconazole. A follow-up PET-CT scan showed increased metabolic activity in the bilateral pulmonary consolidations, thoracic adenopathy, a possible right supraclavicular lymph node, and bilateral inguinal lymph nodes. He underwent a repeat bronchoscopy with EBUS-guided biopsy of the FDG-avid lymphadenopathy, and pathology results indicated granulomatous inflammation. He was evaluated by ophthalmology for uveitis and signs of retinal detachment on brain MRI, as well as nephrology for a progressive decline in kidney function. A renal biopsy showed numerous plasma cells staining for IgG and IgG4, along with storiform interstitial nephritis, consistent with IgG4-related interstitial nephritis. His autoimmune evaluation revealed elevated levels of ANA, double-stranded DNA, RNP antibodies, and various IgG subclasses, including IgG1, IgG3, and IgG4. Considering the biopsy results and the reduced suspicion of an infectious process, he was initiated on immunosuppression treatment with prednisone and rituximab for the IgG4-related disease which resulted in significant improvement in both the patient's symptoms and kidney function. Discussion:In conclusion, this case emphasizes the diagnostic challenges of IgG4-related pulmonary disease, largely due to the nonspecific nature of the respiratory manifestations. In our case, the diagnosis remained unclear despite the patient undergoing both transbronchial and EBUS-guided lymph node biopsies. This highlights the importance of maintaining a high clinical suspicion for this underdiagnosed condition as early treatment can lead to notable recovery.