Thank you to Dr. Johr for joining us as a faculty expert to discuss a new diagnosis of granulomatosis with polyangiitis (GPA). The patient was a 19 year old previously healthy male who initially presented with variable upper respiratory and lower respiratory symptoms for a few months with multifocal pulmonary infiltrates refractory to antibiotics, who then developed glomerulonephritis with acute renal failure.

One important take-away from this case is to always think broadly about the differential without anchoring, and to make sure that your clinical decision-making takes your patient’s demographic and medical background into account. Our patient was a healthy 19 year old male who developed persistent otitis media, followed by persistent laryngitis and then lower respiratory symptoms with imaging demonstrating multifocal opacities. He also had constitutional symptoms and a urinalysis with large blood. He was treated at this point for community-acquired pneumonia — this diagnosis was likely an instinctive reaction to pulmonary consolidations and lower respiratory symptoms, but a previously healthy young male is not the typical host for CAP; furthermore, this diagnosis fails to take the patient’s other presenting signs and symptoms into account.

We discussed the differential for pulmonary-renal syndromes. It is not very long! While it is possible that the pulmonary and renal components demonstrate different disease processes, in most cases pulmonary-renal syndrome is secondary to ANCA-associated vasculitis (MPA, GPA, eGPA), Goodpasture’s (anti-glomerular basement membrane), or other rheumatologic conditions (SLE). Our patient’s clinical history of upper airway disease and his presentation with pulmonary-renal syndrome was clinically very strongly concerning for GPA, and his serologies were consistent with this diagnosis (positive anti-PR3 and c-ANCA).

“ANCA” stands for anti-neutrophil cytoplasmic antibody — these can be positive in a number of conditions, even IBD! Recently, identification of a specific anti-nuclear antibody (ie either anti-MPO or anti-PR3) has become increasingly clinically relevant. As we have discussed previously on this blog in our PAN case, vasculitis is inflammation of the vessels and is typically classified based on size of involved vessels. Small-vessel disease can be sub-categorized by disease mechanism into those caused by immune complex deposition, and those caused by presence of ANCA. Figure below from Jennette et al, Arthritis and Rheumatology.

PAN1

GPA is classically characterized by upper airway involvement and constitutional symptoms, and can commonly have renal involvement as well. This disease can also cause subglottis stenosis, which can be life-threatening and incredibly difficult to treat.  It is usually associated with positive anti-PR3 and c-ANCA.

Treatment strategy depends on severity and organ involvement, and also on the patient’s demographics and comorbidities. In general, induction therapy involves a combination of high dose glucocorticoids and either cyclophosphamide or rituximab. In severe cases, plasma exchange can also be used. Treatment also involves a maintenance phase.

References:

Jennette JC et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 013; 65:1.

 

Advertisements