IgG4 Related Lung Disease: The Great Masquerader

Abstract

IgG4 related lung disease is relatively newly recognized autoimmune disorder which can involve lung parenchyma, lymph nodes, pleura and pulmonary vasculature. Its rarity and the nonspecific presentation often leads to delayed diagnosis. Case: 53 years old male presented with chief complaint of progressively worsening dyspnea, dry cough and hemoptysis since 4 years. Review of system was positive for malaise, anorexia, symptoms of dry eyes and mouth and 20 pounds weight loss in the previous year. He reported 30 pack year smoking history and was being treated by his primary care physician for presumed COPD without much symptomatic improvement. No other occupational or environmental exposures were identified. On physical exam patient appeared chronically ill and on auscultation b/l basilar coarse crackles were noted. Chest radiograph demonstrated bilaterally prominent reticular markings. CT chest showed bulky mediastinal and hilar lymphadenopathy along with diffuse irregular cysts and honeycombing, most marked in lower lobes. PFT was significant for total lung capacity 58% of predicted and DLCO 30% of predicted. Complete blood count, liver and kidney function tests, lipase were within normal limits and autoimmune panel was negative. Bronchoscopy with EBUS FNA and transbronchial biopsies were obtained.The lymph node biopsy was positive for dense infiltration of plasma cells positive for CD138. These plasma cells showed predominant expression of IgG and increased expression of IgG4 (average 80-120 positive cells/HPF). The transbronchial biopsies showed lymphoplasmacytic infiltrates. Serum IgG levels were elevated with IgG4 subclass three times normal limit. Patient was diagnosed with IgG4 related lung disease and treatment with prednisone 40 mg daily was started. Clinical response was noted in 4-5 weeks and repeat IgG and IgG4 titers showed improvement. Prednisone was gradually tapered to 5 mg daily and patient continues to be stable one year from initial diagnosis. Discussion:IgG4 related disease is a rare, often multisystem disorder with increasing recognition. Many entities previously considered as isolated idiopathic organ specific syndromes including autoimmune pancreatitis, Miculicz syndrome, Riedel's thyroiditis, are now considered as IgG4 related disease. The lung involvement can present as solid nodules versus ground glass opacities, bronchovascular and interlobular septal thickening and in advanced cases, honeycombing and fibrosis. Pleural fibrosis may occur. The classic pattern of storiform fibrosis on biopsy is uncommon but strongly suggests IgG4 related disease. Tissue IHC staining often demonstrates elevated IgG and IgG4 levels. The serum IgG4 levels are usually elevated. The diagnosis requires high degree of clinical suspicion with supportive lab findings.