IgG4-Related Disease and Hypertrophic Pachymeningitis

Hypertrophic pachymeningitis (HP) is an inflammatory condition in which the dura mater of the cranium or spine becomes thickened, leading to symptoms that result from mass effect, nerve compression, or vascular compromise. The differential diagnosis of HP includes immune-mediated conditions such as rheumatoid arthritis and vasculitis, malignancies, and infections. Many times, no diagnosis is reached; in such cases, the disease has been described as idiopathic HP. IgG4-related disease (IgG4-RD) is a recently described inflammatory condition known to cause tumefactive lesions at myriad anatomical locations. Both IgG4-RD and idiopathic HP share similar demographics, histopathology, and natural history. We hypothesized that IgG4-RD is a common cause of idiopathic HP.To investigate this hypothesis, we identified all pathology specimens diagnosed as noninfectious HP during 25 years at our institution. Fourteen cases had stained slides and paraffin blocks to permit review of the original hematoxylin and eosin stained slides as well as immunostaining of cell blocks. Recently published consensus guidelines describing characteristic histopathology and the necessary quantity of IgG4+ plasma cell infiltrate were used to diagnose IgG4-RD.Four cases (66.6%) that had been regarded previously as representing idiopathic HP were diagnosed as IgG4-RD; of all the reviewed cases, IgG4-RD represented 29% of cases. Of the remaining cases, 3 cases were associated with granulomatosis with polyangiitis (GPA), 2 with lymphoma, and 1 each with rheumatoid arthritis, giant cell arteritis, and sarcoidosis. Two of the cases could not be diagnosed more precisely and were classified as undifferentiated HP. Clinical history, serologic tests, cerebrospinal fluid studies, and radiology alone could not identify the cause of HP. Rather, biopsy with histopathology and immunostaining was necessary to reach an accurate diagnosis. Significant IgG4+ plasma cell infiltrates were observed in rheumatoid arthritis, granulomatosis with polyangiitis, and lymphoma, underscoring the importance of histopathology in making the diagnosis of IgG4-RD.This case series demonstrates that IgG4-RD may be the most common etiology of noninfectious HP and highlights the necessity of biopsy for accurate diagnosis.Abbreviations: ANCA = antineutrophil cytoplasmic antibodies, CNS = central nervous system, CSF = cerebrospinal fluid, CT = computed tomography, GPA = granulomatosis with polyangiitis, HP = hypertrophic pachymeningitis, HPF = high-power field, IgG4-RD = IgG4-related disease, MRI = magnetic resonance imaging, WBC = white blood cell