IgG4-related disease: a rare but treatable cause of refractory intracranial hypertension

Published on Jun 1, 2016in Practical Neurology
· DOI :10.1136/practneurol-2015-001275
Thomas Williams2
Estimated H-index: 2
(QMUL: Queen Mary University of London),
Monica Marta19
Estimated H-index: 19
(QMUL: Queen Mary University of London),
Gavin Giovannoni75
Estimated H-index: 75
(QMUL: Queen Mary University of London)
Hypertrophic pachymeningitis secondary to IgG4-related disease is a rare but sometimes devastating cause of intracranial hypertension. It has the potential for an excellent response to corticosteroids or rituximab. We discuss the clinical presentation, imaging, histology (with its difficult distinction from lymphoma), management and follow-up of a case, including relapse and re-treatment following an initial response to rituximab.
  • References (18)
  • Citations (4)
#1Terumi KamisawaH-Index: 56
#2Yoh Zen (Kobe University)H-Index: 63
Last. John H. Stone (Harvard University)H-Index: 70
view all 4 authors...
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ and is now being recognized with increasing frequency. IgG4-RD is characterized by a lymphoplasmacytic infiltrate composed of IgG4+ plasma cells, storiform fibrosis, obliterative phlebitis, and mild to moderate eosinophilia. The diagnosis of IgG4-RD unifies many eponymous fibroinflammatory conditions that had previously been thought to be confined to single organs. IgG4-RD lesions ...
368 CitationsSource
#1Renata Hebel (Gdańsk Medical University)H-Index: 1
#2Mirosława Dubaniewicz-Wybieralska (Gdańsk Medical University)H-Index: 9
Last. Anna Dubaniewicz (Gdańsk Medical University)H-Index: 15
view all 3 authors...
Sarcoidosis (SA) is a granulomatous, multisystem disease of unknown etiology. Most often the disease affects lungs and mediastinal lymph nodes, but it may occur in other organs. Neurosarcoidosis (NS) more commonly occurs with other sarcoidosis forms, in 1 % of cases it involves only nervous system. Symptomatic NS occurs but on autopsy study up to 25 % of cases are confirmed. NS can affect central nervous system: the brain, spinal cord and peripheral nerves, and muscles. The diagnosis of neurosar...
41 CitationsSource
#1Mollie N. Carruthers (Harvard University)H-Index: 15
#2Arezou Khosroshahi (Emory University)H-Index: 26
Last. John H. Stone (Harvard University)H-Index: 70
view all 5 authors...
Objectives We evaluated the sensitivity, specificity and positive and negative predictive values of elevated serum IgG4 concentrations for the diagnosis of IgG4-RD. Methods Between 2001 and 2011, 190 unique patients had elevated serum IgG4 measurements. We reviewed electronic medical records to determine the indication for IgG4 measurement and underlying clinical diagnosis. Additionally, we reviewed the records of 190 other randomly selected patients from a pool of 3360 with normal results, to e...
196 CitationsSource
#1Young-Sub Lee (KNU: Kyungpook National University)H-Index: 1
#2Hye Won Lee (KNU: Kyungpook National University)H-Index: 2
Last. Jeong-Hyun Hwang (KNU: Kyungpook National University)H-Index: 12
view all 5 authors...
Immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis, defined as focally or diffusely thickened dura mater and lymphoplasmacytic infiltration with increased IgG4 bearing plasma cells, is a rare disease. Moreover, cases involving bone are even rarer. In this report, the authors describe a case of IgG4-related hypertrophic pachymeningitis involving the skull in a 65-year-old man presenting with generalized tonic seizures. There is a 2.4 cm diameter extra-axial mass at the vertex of the le...
11 CitationsSource
#1Lucy X. Lu (Vandy: Vanderbilt University)H-Index: 1
#2Emanuel Della-Torre (UniSR: Vita-Salute San Raffaele University)H-Index: 14
Last. Stephen W. Clark (Vandy: Vanderbilt University)H-Index: 6
view all 4 authors...
Importance IgG4-related hypertrophic pachymeningitis (IgG4-RHP) is an increasingly recognized manifestation of IgG4-related disease, a fibroinflammatory condition that can affect virtually any organ. It is estimated that IgG4-RHP may account for a high proportion of cases of hypertrophic pachymeningitis once considered idiopathic. Objective To summarize the current knowledge on IgG4-RHP including its pathological, clinical, and radiological presentations. Particular emphasis is placed on diagnos...
94 CitationsSource
#1Akiko Yokoseki (Niigata University)H-Index: 4
#2Etsuji Saji (Niigata University)H-Index: 6
Last. Izumi Kawachi (Niigata University)H-Index: 13
view all 16 authors...
The aim of this study was to elucidate the characteristics, pathogenesis and treatment strategy of hypertrophic pachymeningitis that is associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). We retrospectively investigated clinical, radiological, immunological and pathological profiles of 36 patients with immune-mediated or idiopathic hypertrophic pachymeningitis, including 17 patients with myeloperoxidase-ANCA, four patients with proteinase 3-ANCA, six patients with other ...
53 CitationsSource
#1Emanuel Della-Torre (UniSR: Vita-Salute San Raffaele University)H-Index: 14
#2Laura GalliH-Index: 1
Last. Maria Grazia Sabbadini (UniSR: Vita-Salute San Raffaele University)H-Index: 35
view all 10 authors...
Abstract Diagnosis of IgG4-Related Hypertrophic Pachymeningitis (IgG4-HP) relies on meningeal biopsies, because cerebrospinal fluid (CSF) diagnostic biomarkers are lacking. Here, we determined whether IgG4 intrathecal production could distinguish IgG4-HP from other disorders presenting with HP (OHP). In patients with IgG4-HP, the median CSF IgG4 concentration, IgG4 Index and IgG4Loc were significantly higher than in both controls and OHP. CSF IgG4 levels higher than 2.27 mg/dL identified 100% of...
29 CitationsSource
#1Jun Murakami (University of Toyama)H-Index: 8
#2Shoko Matsui (University of Toyama)H-Index: 19
Last. T Sugiyama (University of Toyama)H-Index: 32
view all 10 authors...
A 54-year-old woman with suspected low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type of the eyelids underwent rituximab-containing chemotherapy. She initially responded to the rituximab therapy, but later experienced two recurrences over a 3-year period. Biopsy specimens and a review of her previous histology revealed that she had had immunoglobulin G4-related disease at the initial presentation. Although IgG4-related disease seems to respond well to rituximab therapy, long-ter...
18 CitationsSource
#1Zachary S. WallaceH-Index: 18
Last. John H. StoneH-Index: 70
view all 8 authors...
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) i...
91 CitationsSource
#1Vikram Deshpande (Harvard University)H-Index: 90
#2Yoh Zen (University of Cambridge)H-Index: 63
Last. John H. Stone (Harvard University)H-Index: 70
view all 41 authors...
IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and—often but not always—elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4–7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Ital...
1,120 CitationsSource
Cited By4
#1Cléa Melenotte (AMU: Aix-Marseille University)H-Index: 8
#2Julie Seguier (AMU: Aix-Marseille University)H-Index: 2
Last. Nicolas Schleinitz (AMU: Aix-Marseille University)H-Index: 28
view all 23 authors...
Abstract Pachymeningitis is rare, either idiopathic or secondary to inflammatory disorders, after tumoral, surgical or infectious causes have been excluded. The fibroinflammatory IgG4-related disease is one of the etiologies of pachymeningitis with only few cases reported yet. From a single referral regional center, we evaluated the frequency of IgG4-related disease as the cause of inflammatory pachymeningitis in 10% of cases. From a National case registry of IgG4-related disease the pachymening...
#1Gonçalo CaçãoH-Index: 1
#2Margarida CalejoH-Index: 1
Last. Joana DamásioH-Index: 5
view all 9 authors...
Background Hypertrophic pachymeningitis (HP) is characterized by cranial and/or spinal thickening of the dura mater with or without associated inflammation. Neuroimaging studies reveal dura mater thickening and focal or diffuse contrast enhancement. It is described in association with trauma, infections, tumors, autoimmune/inflammatory diseases, and cerebrospinal fluid hypotension syndrome, with some cases remaining idiopathic.
1 CitationsSource
#1Mahmoud A. AbdelRazek (Harvard University)H-Index: 1
#2Nagagopal Venna (Harvard University)H-Index: 16
Last. John H. Stone (Harvard University)H-Index: 70
view all 3 authors...
Summary IgG4-related disease can involve nearly any organ system, including the central and peripheral nervous systems. The pathology findings are consistent from organ to organ, but careful clinicopathological correlation is necessary to establish the diagnosis. Many non-neurological and neurological inflammatory conditions, previously regarded as idiopathic in nature, are now recognised to fall within the spectrum of IgG4-related disease. The condition is highly treatable, but probably remains...
11 CitationsSource
#1Kaiyuan Huang (ZJU: Zhejiang University)H-Index: 2
#2Qingsheng Xu (ZJU: Zhejiang University)H-Index: 4
Last. Jianwei Pan (ZJU: Zhejiang University)H-Index: 8
view all 6 authors...
Backgound and Importance Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare fibrosing inflammatory process involving the dura mater. Currently, there is no consensus on the treatments for IHCP, and the usefulness of immunosuppressive agents as a first-line option remains controversial. Cerebral venous sinus occlusion (CVSO) and cerebral venous sinus thrombosis (CVST) secondary to IHCP, which may cause progressive intracranial hypertension and venous obstructive parenchymal lesions,...
2 CitationsSource