Case Presentation:

54-year-old male who presents to clinic complaining of blurry vision and dizziness. Past medical history significant for bilateral intraorbital masses causing proptosis, hypothyroidism and hypertension.  Physical examination remarkable for restricted extraocular muscle movements and mild proptosis.

He was diagnosed with intraorbital masses 9 years ago, s/p 3 biopsies. Last MRI showed bilateral orbital mass causing exophthalmos and ptosis. Patient developed worsening proptosis with restriction of extraocular muscle function and decreased vision for which he underwent superior orbitotomy with tumor debulking and incisional biopsy of the lesion on the right side 3 months ago. Biopsy showed connective tissue with fibrosis, which contains chronic lymphoplasmacytic inflammatory infiltrate. By immunohistochemistry (IHC), lymphoid cells consist of a near equal mixture of CD20 positive  B cell, CD3 positive T cells, and T cells coexpress CD5 and BCL2, CD20/CD5, and CD20/BCL2 coexpression is not appreciated.  Cyclin D1 is negative in lymphoid cells.  CD138 positive plasma cells.  These support the interpretation of a nonspecific, chronic inflammation. Patient received prednisone treatment which was tapered over 3 weeks, proptosis and eye swelling had some improvement. Patient was referred to rheumatology clinic for possible IgG4 disease deposition disease.

Further workup revealed elevated IgG4 (283 mg/dl), hepatitis B core and surface antibody positive. Results of other laboratory studies including quantiferon-TB, AFB smear and culture,  ACE level, anti-CCP, RF, ESR, CRP, complement C3 and C4, c-ANCA, p-ANCA, anti-SSA and anti-SSB, anti-RNP, anti-dsDNA, free kappa light chains and free lambda  were negative or within normal limits. Protein electrophoresis was unremarkable. Flow cytometric immunophenotyping showed no evidence of a B-cell lymphoproliferative disorder or atypical T-cell lymphoid population. The patient was started on rituximab to be followed up in clinic.

Discussion:

IgG4-related disease (IgG4-RD) is categorized by idiopathic tissue infiltration of IgG4-producing plasma cells and irreversible fibrosis.  IgG4-RD most commonly affects the pancreas, causing a sclerosing pancreatitis. Onset of visual disturbances often is not the presenting symptom. Ophthalmic disease may include involvement of the orbits themselves and/or surrounding adnexal structures. 

Several new criteria have recently been established to help delineate this from idiopathic orbital myositis (IOM), a disease process with similar presentation: (1) identification of > 10 IgG4-plasma cells per HPF, (2) > 135 mg/dl serum IgG4 concentration, and (3) abnormally elevated IgG4+ to IgG+ plasma cell ratio.  On imaging, computerized tomography may demonstrate increased signal attenuation, while MRI may show non-specific intensities on both T1- and T2-weighted images.  PET/CT has been showed to play a role in identifying multi-organ disease.

Current medical management relies on long-term corticosteroid therapy with good control.  However, relapse is also quite frequent upon discontinuation.  In cases of refractory IgG4-RD ophthalmic disease, addition of newer immunomodulatory agents such as rituximab to the treatment regimen have shown to be markedly effective in symptom control.

 Conclusions:

IGG4-RD is a rare systemic fibro-inflammatory disorder. To our knowdlege this is the first case report of isolated IgG4-RD.