pachymeningitis is a rare feature of wegener 's granulomatosis ( wg ) and an uncommon initial manifestation of the disease .
we demonstrate that pachymeningeal lesions refractory to conventional therapy can resolve completely by the addition of rituximab ( rtx ) to standard remedies .
this case also illustrates that besides global headache , wg - related pachymeningitis may occasionally manifest itself by lateralized pain and cranial nerve involvement [ 25 ] .
in 2004 , a 27-year - old caucasian female was admitted for persistent right - sided ear , jaw , and neck pain , with recent advent of tinnitus , hearing loss , and nasal sores .
a ct - scan showed mucosal thickening of the maxillary sinuses without bony erosions . a biopsy from nasal mucosa showed vasculitis and granuloma formation .
bronchoalveolar lavage ( bal ) fluid was negative for bacterial growth , mycobacterial pcr , and malignant cells .
however , the patient tested positive for pr-3 anca ( 49  u / ml , < 10 ) .
blood cell counts were normal , crp below 15  mg / l , creatinine clearance , and urinalysis were normal . based on these findings , the patient was diagnosed with wegener 's granulomatosis .
cerebral magnetic resonance imaging ( mri ) with gadolinium showed infratentorial , meningeal thickening along the right cerebellar tentorium , the cerebellopontine angle ascending into the right foramen jugulare . besides , a thrombus extending from the right sinus transversus to bulbus venae jugularis was diagnosed .
based on these findings , wegener related pachymeningitis was suspected although not histologically confirmed .  
induction treatment included intravenous methylprednisolone pulses ( 1  gram / day for 3 days ) , plasma exchange on 5 consecutive days , and oral cyclophosphamide .  
low molecular weight heparin and warfarin were added for prophylaxis against progression of cerebral venous thrombosis .
however , the cyclophosphamide dosing target at 2  mg / kg could not be achieved due to debilitating nausea and liver toxicity , and she suffered from persistent cervicocranial pain despite normal crp , pr-3 anca seroconversion , and partial regression of meningeal pathology by mri .   in december 2006 , the patient complained of diplopia .
a repeat mri scan showed marked progression of the infratentorial dura - meningeal enhancement ( figure 1(a ) ) , whereas partial revascularisation of the transverse sinus was noted .
azathioprine 50  mg / daily was added to the current prednisolone medication ( 50  mg daily ) , but it had to be discontinued after 3 weeks due to intolerable nausea and elevated liver enzymes . due to similar drug toxicity ,
methotrexate 15  mg weekly added to daily 40  mg prednisolone medication was abandoned after 2 months treatment . in february 2007 , rituximab was added as follows : 4 weekly rituximab infusions ( 375  mg / m ) combined with i.v .
cyclophosphamide ( 500  mg / m ) on a separate day . already within 1 week after the first infusion , diplopia and neck pain had vanished .
a follow - up mri at 6 months showed partial regression of the meningeal pathology ( figure 1(b ) ) , and chest ct revealed complete regression of the lung infiltrate .
subsequently , relapsing neck and ear pain with concomitant epistaxis , nasal sores or sinusitis occurring at 810 months intervals have been successfully brought into remission 4 times using the treatment protocol described above .
an mri - scan in february 2009 showed complete regression of meningo - dural enhancement ( figure 1(c ) ) .
global headache is the most frequent manifestation of wg related pachymeningitis although the condition may occasionally manifest itself with lateralized pain and cranial nerve involvement like in the present case [ 25 ] .
signs and symptoms of meningeal involvement in wg may result from different disease processes including vasculitis , bony destruction by invasive inflammatory cell infiltration or intraparenchymal granuloma formation [ 3 , 5 ] . besides , the increased risk of complicating venous thromboembolism reported recently should be considered as illustrated by the sinus thrombosis encountered in this case .  
the relative contribution of these pathways can not be settled in this case , but the absence of destruction and granulomatous lesions by mri favours a dominant role of vasculitis .
although conventional therapy using oral prednisolone and cyclophosphamide was followed by regression of the meningeal lesions seen on mri , a parallel clinical response was not achieved .
probably , this is due to the submaximal dosing of these agents due to adverse effects .  
based on reports on favourable responses of rtx in refractory wg , we decided to add rituximab to i.v .
although the exact mechanism behind the response to rtx in wg patients is unknown , it is likely that targeting cd20 + b - cells , which are precursors of anca - producing plasma cells , is important as evidenced by the long - term pr-3 anca seroconversion observed in this patient .  
successful treatment of wegener 's meningitis has been reported in the past ( table 1 ) [ 710 ] .
this case is unique by demonstrating that multiple rtx cycles can be administered safely and effectively , resulting in long - term complete clinical and imaging remission despite substantially reduced immunosuppressive comedication , glucocorticoids in particular ( figure 2 ) .
the effect of each single agent applied in the present combination protocol can not be determined . however , as shown in figure 2 , a marked reduction of the median pdn and cyc doses was observed during rtx treatment as compared with the pre - rtx period , thereby supporting the notion of a specific effect of rtx on wg disease pathways .
this view is further supported by the need for repeat infusions ( figure 2 ) .   in conclusion
, this paper illustrates that wg may present with localized meningeal involvement and that rituximab added to conventional agents has a steroid sparing effect and can lead to clinical and imaging remission in wegener - related pachymeningitis .
 a 27-year - old woman 
 was admitted for intractable right - sided neck , 
 ear , and jaw pain with gradual development of 
 tinnitus and hearing loss . 
 a cerebral mri showed 
 meningo - dural enhancement , and additional 
 diagnostic workup revealed a right pulmonary 
 infiltrate and positive pr-3 anca . 
 biopsies from 
 nasal mucosa and lung showed chronic 
 inflammation with granuloma formation . based on 
 these findings 
 the patient was diagnosed with 
 wegener 's granulomatosis with 
 pachymeningitis . 
 there was no clinical response 
 to oral prednisolone and cyclophosphamide , but 
 complete clinical and imaging remission was 
 achieved by adding rituximab . 
1. Introduction
2. Case Report
3. Discussion