Background/Purpose: 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.

Methods: To investigate this hypothesis, we identified all pathology specimens diagnosed as HP in a 25-year time span at our institution. Fourteen cases had extant stained slides and cell blocks to permit review of the original hematoxylin and eosin (H&E) stained slides was 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. 

Results: Four cases (29%) that had been regarded previously as representing idiopathic HP were diagnosed as IgG4-RD (Table 1).  Of the remaining cases, there were three cases associated with granulomatosis with polyangiitis (GPA), two with lymphoma, and one 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.

Conclusion: This case series demonstrates that IgG4-RD may be the most common etiology of non-infectious HP and highlights the necessity of biopsy for accurate diagnosis.  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.   

Table 1:

Case	Diagnosis	Site	Age	Gender	Symptoms	Lympho-plasmacytic Infiltrate	Storiform Fibrosis	Phlebitis	Eos	Granulomas	Giant Cells
1	IgG4-Related Disease	Intracranial dura	50	Female	Seizures	Y	Y	N	N	N	Y
2	IgG4-related Disease	Intracranial dura	52	Female	Headache	Y	Y	Y	Y	Y (few)	N
3	IgG4-related Disease	Intracranial dura	39	Male	Headache & arm numbness	Y	Y	N	N	N	N
4	IgG4-related Disease	L5 nerve root dura	32	Male	Weakness	Y	Y	Y	Y	N	N
5	Granulomatosis with Polyangiitis	T2-T8 dura	59	Female	Sensory abnormalities & urinary retention	Y	N	N	Y	Y	Y
6	Granulomatosis with Polyangiitis	Intracranial dura	75	Female	Gait instability	N	Y	N	N	N	Y
7	Granulomatosis with Polyangiitis	Intracranial dura	55	Male	Painful diplopia	Y	Y	N	N	Y	Y
8	Rheumatoid Arthritis	Intracranial dura	58	Female	Ataxia, numbness & visual loss	Y	N	N	N	Y	Y
9	Giant Cell Arteritis	Intracranial dura	59	Male	Central DI	N	N	N	N	N	N
10	Sarcoidosis	Intracranial dura	67	Male	Nausea, vomiting & ataxia	Y	N	N	N	Y	N
11	Lymphoma	Intracranial dura	52	Male	Headache & dizziness	Y	N	N	N	N	N
12	Lymphoma	Intracranial dura	61	Female	CN III Palsy	Y	N	N	N	N	N
13	Undifferentiated	Intracranial dura	44	Female	Headaches & thrombosis	Y	N	N	N	N	Y
14	Undifferentiated	Intracranial dura	75	Male	FUO, gait instability & eye pain	N	N	N	N	N	N

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