A considerable number of patients with lacrimal gland swelling fall under IgG4-Related Dacryoadenitis

The Japanese first described the disease in association with primary pancreatitis as "autoimmune pancreatitis (AIP)", where patients had elevated serum IgG4 levels. Characteristic serologic and histopathologic features of IgG4-RD were then detected in various extra pancreatic sites. Many pathologic conditions previously considered separate and unrelated disorders are part of the IgG4-RD spectrum.

Orbital involvement is a common entity in IgG4-RD (Known as IgG4-related ophthalmic disease [IgG4-ROD]) as an isolated condition or part of the systemic disease. The most frequently involved site was the lacrimal glands, which was also one of the earliest reported extra pancreatic manifestations of IgG4-RD. Other ocular involvement patterns included the trigeminal nerve, extraocular muscles (EOMs), and orbital mass lesions.

Authors Salama et al carried out a study to report clinical, serological, and histopathological findings in Egyptian patients with dacryoadenitis associated with IgG4-RD. They retrospectively revised medical records of patients presented to Al-Azhar University Hospitals with lacrimal gland (LG) swelling between June 2016 and February 2022. Study included patients with definite IgG4-related disease (IgG4-RD) diagnosis and excluded those with possible, probable, or unlikely IgG4-RD based on The Japanese Ministry of Health, Labour, and Welfare's 2011 guidelines.

Sixteen cases were included in the study (Fourteen females and two males, mean age 39.2±12.2 years); Seven cases met the criteria of Mikulicz disease, and nine cases met full clinical, serological, and histopathological criteria.

Mean reported serum IgG was 1792.5 ± 313.7 (range 1063–2134) mg/dl, mean serum IgG4 was 576.25±215.3 (range 112–841) mg/dl, and mean Serum IgG4/IgG ratio was 31.9 ± 12.4%.

The mean number of IgG4+ plasma cells/HPF was 74 ± 21.2, and the mean IgG4+ plasma cell percentage was 55 ± 9.7%. Serum IgG4 level showed a positive correlation to tissue IgG4+plasma cell percentage, while serum IgG4/IgG ratio positively correlated to both percentage and number of IgG4+plasma cells. Steroids had a good initial response, but recurrences were common.

The patients' ages in the study ranged from 8 to 55 years. Gender distribution in this study was noticeable with a female to male ratio of 7:1. Dacryoadenitis was reported as the most common manifestation of IgG4-ROD. The cutoff diagnostic tissue criteria are controversial.

In this study, the number of IgG4+ plasma cells ranged from 40 to >100/HPF, and the ratio of IgG4+/IgG+ plasma cells ranged from 40% to 70%. Study also reported variable eosinophilic infiltration and excessive fibrosis with a storiform pattern in all specimens, but obliterative phlebitis was not detected. Similarly, a serum IgG4 level of >135mg/dl is generally accepted as one of the three primary diagnostic criteria of IgG-RD. Other serological clues were also suggested for the diagnosis of IgG4-RD. The normal IgG4/IgG ratio is about 5–6%; an elevated IgG4/IgG ratio.

Lacrimal glands' radiological findings in the cases of IgG4-related dacryoadenitis were indistinct from radiologic features of dacryoadenitis due to other causes such as an idiopathic orbital inflammatory disease. Orbital radiographs were valuable for detecting other IgG4-ROD features such as enlarged EOMs, enlarged orbital nerves, and orbital soft tissue masses. None of the reported cases had enlarged orbital nerves or orbital masses.

Corticosteroids have been the mainstay of treatment. Conventional oral steroid regimens and pulse steroid therapies were both used. The response is often excellent, but relapses are common. Immunosuppressant agents, including azathioprine, methotrexate, and mycophenolate, have been involved in managing IgG4-RD as steroid-sparing or in cases of relapses. Data has shown that Rituximab, an anti-CD20 monoclonal antibody, can be used successfully to treat IgG4-RD. Radiotherapy in low doses has been reported in the treatment of IgG4-ROD in a small number of cases.

Suthors got a 68.75% primary success rate with oral steroids, cases with a suboptimal response, and those with relapses had immunosuppressive drugs (azathioprine, methotrexate), with favorable results. Medications, doses, and duration of treatment were prescribed in collaboration with rheumatologists. They have used pulse steroid therapy in 2 cases with an acute presentation. None of the cases had received radiotherapy. The reported recurrence rate in study was 56.25% within 4–23 months. Other recurrent cases may evolve on longer follow-up.

A significant proportion of cases with lacrimal gland swelling may be part of IgG4-RD. Laboratory work, histopathology, and systemic workup are essential for proper management. The disease had a higher predilection in females. The serum IgG4/IgG ratio may be of greater diagnostic value than the serum IgG4 level. Cases require long-term follow-up due to the high recurrence rate.

Source: Salama et al; Clinical Ophthalmology 2022:16 2765–2773

https://doi.org/10.2147/OPTH.S378583