IgG4 Related Disease

We discussed a case of a middle-aged man with IgG4-related disease (with salivary gland, ?pulmonary, and renal involvement) recently started on Rituximab given drug toxicities from previous prednisone and azathioprine, now presenting with several days of fevers, dry cough, and watery diarrhea, found to have progressive hypoxia and evolving bilateral multifocal consolidations in a bronchovascular distribution/organizing pneumonia and diffuse ground glass opacities/non-cardiogenic edema on CT--overall thought to be related to pulmonary drug toxicity from the Rituximab. 

Clinical manifestations of IgG-4 related disease. 

Clinical manifestations of IgG-4 related disease. 

A few learning points from the case: 

1) IgG4 related disease

  • A recently recognized disease, evolving in the literature since about 2003
  • Pathogenesis is incompletely understood, but it generally it is an immune-mediated inflammatory and sclerosing disease, characterized by a mass-forming (tumefactive) lesions, infiltration of IgG4 positive plasma cells, and often an elevated serum IgG4 (about 70%, this is also elevated in multiple other conditions and is non-specific).
  • Most common manifestations are autoimmune pancreatitis, parotid/lacrimal swelling, and lymphadenopathy. Additionally, sclerosing cholangitis and retroperitoneal fibrosis are frequent manifestations.
  • The condition must be confirmed histopathologically and patients often respond early in the course to glucocorticoid therapy, but may require multiple immunosuppressive agents. 

2) Rituxumab: 

  • An anti-CD20 monoclonal antibody with growing use in treating autoimmune disorders
  • Has been, albeit rarely, associated with significant pulmonary toxicity including interstitial pneumonitis, organizing pneumonia, and even ARDS.
  • Check out a systematic review about this from Oxford Journal's Rheumatology 2012 here

3) Organizing pneumonia: 

  • A pathological pattern that is not specific for any disorder or cause, but reflects one type of inflammatory process resulting from lung injury
  • The particular pathological hallmark of a characteristic clinicoradiological entity called cryptogenic organising pneumonia.
  • Preferred to the other name used for this condition—namely, idiopathic bronchiolitis obliterans with organising pneumonia (BOOP)—which may be confused with other types of bronchiolar disorders, particularly constrictive bronchiolitis obliterans
  • Has an association with conditions such as infectious pneumonia, lung abscess, empyema, lung cancer, bronchiectasis, broncholithiasis, chronic pulmonary fibrosis, aspiration pneumonia, ARDS, pulmonary infarction
  • Check out a nice review from BMJ Thorax here