The first case of ILD associated with IgG4-related disease was reported in 2004 in a 63-year-old man with AIP . In western countries, similar cases of IgG4-related ILD in patients with AIP were reported in 2006 .
In 2008, Takato et al. reported the first case of isolated IgG4-related ILD in a 59-year-old man who was found to have ground-glass opacities and reticular shadows with honeycomb-like changes and traction bronchiectasis in the lower lobes on chest CT scan. Pathological examination of a lung biopsy obtained by VATS revealed findings corresponding to fibrotic nonspecific interstitial pneumonitis (NSIP). Subsequent immunostaining for IgG4 showed infiltration with numerous IgG4-positive plasma cells. Serum IgG4 levels were increased. This patient did not present with AIP and the authors suggested that IgG4-related ILD could occur unrelated to AIP .
More recently, another case of isolated IgG4-related interstitial pneumonia was reported in a 75-year-old male patient who presented with a two months history of cough and shortness of breath upon exertion. A chest CT scan revealed bilateral diffuse ground-glass opacity with traction bronchiectasis, especially in the bilateral lower lobes. Serum IgG4 levels, which were screened by chance, were increased. Pathologic examination of VATS biopsies revealed infiltration of mostly IgG4 positive plasma cells. There was thickening of the bronchovascular bundles and alveolar septa but neither fibrotic nor vascular lesions were observed. The authors hypothesized that IgG4 plays an important role in the pathogenesis of some cases of interstitial pneumonia initially diagnosed as idiopathic NSIP, and that these interstitial pneumonias may be regarded as a new entity that should be differentiated from idiopathic NSIP .
The present case, to our knowledge, is the third case of isolated IgG4-related ILD ever reported and the first observed in western countries. Similar to the cases reported before [5, 6], AIP was not clinically apparent in this patient and symptoms as well as radiologic findings and serum IgG4 levels responded well to steroid treatment. Histological pattern was similar to UIP, unlike the two cases published before where NSIP pattern was present. Imaging was characterized by consolidations, lymphadenopathy and pleural effusions, whereas reticular shadows and ground glass opacities were predominant in the previous two cases.
Although a histological finding of UIP often corresponds to a clinical diagnosis of idiopathic pulmonary fibrosis (IPF), it is known that a histological pattern similar to UIP, like in the present case, can also occur in clinical conditions other than IPF . In fact, chest CT findings in this case were strikingly different from the radiologic pattern expected in IPF. Eventually, immunohistology, serum IgG4-concentrations and radiologic features met all diagnostic criteria recently proposed for IgG4-related disease, which led to the definite diagnosis of IgG4-related ILD . Consistently, the rapid and significant response to steroid treatment supported the diagnosis.
Classification criteria and nomenclature of IgG4-RD are currently being established . We doubt that isolated IgG4-related ILD needs to be classified as a new separate entity among idiopathic interstitial pneumonias (IIP), as proposed elsewhere [5, 6]. Assuming that IgG4-related ILD may have the same pathogenesis as IgG4-related disease manifesting in other organs, it could be considered as a part of the spectrum of systemic IgG4-related sclerosing diseases, even when no other organ involvement may be clinically apparent at the time of diagnosis. We therefore suggest that IgG4-related ILD may be classified as “diffuse parenchymal lung disease (DPLD) of known cause or association”. Systematic data on the prevalence and incidence of IgG4-related ILD is needed, and further studies addressing the evaluation of IgG4 concentration in tissue and serum in patients with ILD may shed further light on the association of IgG4 with ILD and the underlying pathophysiology.