# Outologic Manifestations of IgG4-Related Disease: Literature Review and Report of Two Cases
## 4 Results  
In addition to the two cases presented here, senenteen more cases of IgG4-RD with mastoid involvement were reported between 2012 and 2022. A total of nineteen cases included 5 males and 14 females, ages 45 \(\pm\) 11 years (mean \(\pm\) SD). The most common clinical presentations were otitis media and mastoiditis (8, 42% and 7, 37%, respectively); three patients (15.7%) had a clinical presentation of inflammatory pseudotumor.  
All patients underwent surgical intervention that included mastoidectomy and surgical site biopsies. Five of the nineteen patients (26.4%) required repeated surgical intervention. Importantly, eight of the cases (42%) involved extra otologic sites: three cases of cranial fossa (middle and posterior), three cases of meningitis, and one case of cervicitis with parotiditis.  
Serum IgG4 levels were available in 12 out of 19 patients. Values were elevated in seven patients (>135 mg/dL; 229 \(\pm\) 50.4 mg/dL) and normal in five patients.  
Symptomatology, pharmacological treatment, and chronology of the disease are described in Figure 6. The most frequent symptoms included hearing loss, otalgia, tinnitus and headache as reported in nine, six, and five patients, respectively. Otorrhea was reported in three patients (Figure 5(a)). The clinical presentation of IgG4-related disease in the ear was not specific nor compatible with other infectious and inflammatory processes of the middle ear or mastoid bone.  
All patients underwent CT scans, while MRI was further performed in seven patients, as part of the pre-operative management. Soft tissue opacification and extensive destruction of mastoid bone were noted in 12/19 patients (63%). In two cases, imaging concluded the presence of an inflammatory pseudotumor.  
The biopsies obtained from all cases were suggestive of IgG4-RD. Dense lymphophasmacytic cells infiltrate were reported in all, while storiform fibrosis and obliterative phlebitis was noted in 14/19 cases (73.6%) and 6/19 (31.5%) cases, respectively. Information regarding IgG4/IgG ratio was published in ten cases, averaging 40% IgG4/IgG ratio. Absolute counts of IgG4 were recorded in nine cases, averaging 78 \(\pm\)68.5 cells per high power field (HPF).  
Figure 6: _Cont._Treatment data (Figure 6b) were reported in all 19 case reports. In most cases, initial therapeutic management, prior to the pathological diagnosis, included antibiotics and symptomatic treatment. Except for three cases, treatment was initiated only after a final pathologic diagnosis had been rendered. The most common treatment was corticosteroids, followed by immunosuppressive agents such as rituximab, cyclophosphamide, and methotrexate. Combined regimens of corticosteroids and rituximab/methotrexate were reported in three of the cases. In these three cases, the treatment was given only after the biopsy (in order to avoid potential obscure of histologic picture). Generally, it can be said that symptom relief and recovery were recorded quickly under treatment. This fact retrospectively helped reinforce the diagnosis based on the histopathological laboratory results.  
Figure 6: Clinical features of IgG4 related mastoiditis.  
Patients frequently followed an extended clinical course, from presentation to the hospital to a final diagnosis (Figure 6c). Time elapsed to diagnosis was reported in fifteen of the patients. In six cases it lasted more than 12 months to reach a diagnosis.