Introduction: IgG4-related pachymeningitis is a serious autoimmune condition that can present with symptoms of mass effect and related focal deficits. According to a general consensus on management of IgG4-related diseases, the first-line therapy is steroids and chemotherapy, such as methotrexate. We describe a patient with IgG4-related pachymeningitis in whom steroid use was contraindicated and methotrexate was ineffective.
Methods: A 54-year-old woman presented to her neurologist with a three-year history of gradual onset sensorineural hearing loss, right side greater than left, and worsening left sided headaches and dizziness. Given the patient’s increasingly debilitating headaches, dizziness, and lack of diagnosis despite an exhaustive evaluation, she underwent a left temporal craniotomy and biopsy of the dural lesion. Stereotactic navigation was used to plan the craniotomy. A perforator drill was used to make a burr hole, after which a craniotome was used to turn the bone flap. With the aid of stereotactic navigation, the most thickened and abnormal dura was identified.
Results: Grossly, the dural sample was white, thick and avascular. Histopathological analysis revealed a striking number of IgG4-positive plasma cells (greater than 200 per high-powered field in more than 5 high-powered fields; IgG4/IgG ratio estimated at 58%). Postoperatively, the patient responded well to steroids; however, their continued administration was contraindicated due to her history of gastrointestinal surgery. Methotrexate dose was increased and continued for months with suboptimal response. During the course of her treatment, the patient presented to the emergency department with receptive and expressive aphasia, slurred speech, right-sided neglect, and loss of sensation. After a single infusion of rituximab and initiation of anticonvulsants, her symptoms resolved.
Conclusions: Although IgG4 disease generally responds well to steroids and chemotherapeutic agents, the clinician must always take into account the patient’s individual circumstances. In this case, early rituximab might have been the most appropriate treatment
Patient Care: The general consensus on treatment of IgG4-related diseases is that administration of steroids typically produces a favorable response with attenuation of clinicoradiological signs and symptoms. In our case, where high dose steroid use was relatively contraindicated, oral methotrexate was administered with escalating dose up to 25 mg per week; however, as evidenced by the worsening of the patient’s symptoms and eventual episode of aphasia and sensorimotor deficits, response to methotrexate was suboptimal. Rituximab treatment was associated with resolution of neurological symptoms in our patient. Clinicians should thus consider early administration of rituximab treatment in patients with aggressive forms of IgG4-related pachymeningitis.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Review the etiology of IgG4-related pachymeningitis. 2) Understand the importance of neurohistopathology in the diagnosis of IgG4-related pachymeningitis. 3) Recognize that the patient's individual circumstances must always be the basis for choosing the most appropriate treatment.
References: 1. Perez Alamino R, Espinoza LR, Zea AH. The great mimicker: IgG4-related disease. Clin Rheumatol. 2013;32(9):1267-1273. doi:10.1007/s10067-013-2326-z.
2. Stone JH, Khosroshahi A, Deshpande V, et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum. 2012;64(10):3061-3067. doi:10.1002/art.34593.
3. Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. The Lancet. 2015;385(9976):1460-1471. doi:10.1016/S0140-6736(14)60720-0.
4. Mahajan VS, Mattoo H, Deshpande V, Pillai SS, Stone JH. IgG4-related disease. Annu Rev Pathol. 2014;9:315-347. doi:10.1146/annurev-pathol-012513-104708.
5. Lu LX, Della-Torre E, Stone JH, Clark SW. IgG4-related hypertrophic pachymeningitis: clinical features, diagnostic criteria, and treatment. JAMA Neurol. 2014;71(6):785-793. doi:10.1001/jamaneurol.2014.243.
6. Wallace ZS, Carruthers MN, Khosroshahi A, et al. IgG4-Related Disease and Hypertrophic Pachymeningitis: Medicine (Baltimore). 2013;92(4):206-216. doi:10.1097/MD.0b013e31829cce35.
7. Khosroshahi A, Wallace ZS, Crowe JL, et al. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol Hoboken NJ. 2015;67(7):1688-1699. doi:10.1002/art.39132.
8. Choi S-H, Lee SH, Khang SK, Jeon SR. IgG4-related sclerosing pachymeningitis causing spinal cord compression. Neurology. 2010;75(15):1388-1390. doi:10.1212/WNL.0b013e3181f73614.
9. Kosakai A. [Central and peripheral nervous system involvement in immunoglobulin G4-related disease]. Brain Nerve Shinkei Kenkyu No Shinpo. 2013;65(11):1343-1352.
10. Lindstrom KM, Cousar JB, Lopes MBS. IgG4-related meningeal disease: clinico-pathological features and proposal for diagnostic criteria. Acta Neuropathol (Berl). 2010;120(6):765-776. doi:10.1007/s00401-010-0746-2.