**8. Treatment**

*Chronic Autoimmune Epithelitis - Sjogren's Syndrome and Other Autoimmune Diseases...*

*Extensive fibrosis with storiform appearance and chronic inflammatory infiltrate (H*&*E, 400×).*

*Extensive fibrosis with storiform appearance and chronic inflammatory infiltrate (H*&*E, 200×).*

*Immunohistochemical staining for CD138 revealed that majority of the cells are plasmocytes (hematoxylin, 200×).*

**82**

**Figure 4.**

**Figure 3.**

**Figure 2.**

Treatment of IgG4-RD is based on the experience of the attending physicians and opinions of the experts, as there are no large controlled clinical trials covering this problem so far. Moreover, the exact molecular pathomechanism of IgG4-RD is not known, so determination of targeted therapies is not possible at the moment. In every patient, treatment should be individually planned, depending on the location and organ damage, coexisting diseases and contraindications to immunosuppressive treatment. Another aspect of IgG4-RD therapy is that the disease tends to recur in case of treatment withdrawal. In the group of patients with the highest recurrence rate, increased baseline level of serum IgG4, IgE and eosinophils was observed [5]. At present, the experts recommend pharmacologic treatment in patients with active lymphoplasmatic infiltrations in histopathological examination. Surgery may be considered in patients with a long-lasting disease with predominant fibrosis, poorly responding to basic treatment [13, 83]. Therapy including careful observation without rapid initiation of treatment may be considered in moderate lymphadenopathy and with moderate enlargement of the submandibular salivary gland. In case of subclinical forms with involvement of the bile ducts, kidneys, aorta, retroperitoneal fibrosis, pancreas, pachymeningitis, pericarditis, treatment must be started even with a lack of clinical symptoms due to progressive, irreversible organ damage.

According to international guidelines of IgG4-RD treatment, the first-line medicines are glucocorticoids: oral prednisone, at an initial dose of 0.6 mg/kg daily maintained for 2–4 weeks and gradually reduced for 3–6 months [83, 84]. In Japanese guidelines, glucocorticoids in small maintenance doses (5–10 mg daily) are recommended even for 3 years [88]. In case of recurrences, repeated administration of glucocorticoids is proposed in the above schedule [83]. Most of the patients show fast improvement after glucocorticoid use. As soon as after several weeks of treatment, improvement of functional parameters of the involved organs is observed, with a reduction of the infiltration mass and a decrease of serum IgG4 concentration.

There are no publications which would constitute guidelines for the application of disease modifying antirheumatic drugs in patients not responding to or not tolerating treatment with glucocorticoids or who experience frequent disease recurrences. In 46% of patients with IgG4-RD who have their glucocorticoid doses decreased, the disease recurs [89]. As in other rheumatic diseases, the disease modifying antirheumatic drugs are tried in such cases. The adjunctive therapy has so far applied most drugs used in rheumatology, including methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide. However, the results and their efficacy are different. Adjunctive treatment with disease modifying antirheumatic drugs is currently based mainly on the experience of attending physicians and is experimental. At present, there are no well-designed clinical trials summarizing this problem. Moreover, the disease modifying antirheumatic drugs were always used as adjunctive treatment to glucocorticoid therapy and not as first-line therapy, therefore their efficacy is even more difficult to evaluate. In 2017, a summary of observations in patients treated with glucocorticoids vs. glucocorticoids and cyclophosphamide orally was published [90]. It turned out that a combination of disease modifying antirheumatic drugs decreased the risk of disease recurrence by 70% as compared to the group treated with glucocorticoid monotherapy.

In case vascular location and lesions in the aorta, there are no explicit guidelines concerning treatment. Similarly as in other forms of IgG4-RD, steroids are used, most commonly prednisone at a dose of 0.6 mg/kg daily. This dose is gradually reduced to the maintenance dose of 5 mg/kg daily. There are no guidelines concerning therapy duration. Steroid administration does not protect against development and progression of aneurysms in patients in whom vascular wall widening was found initially [9, 80]. In this group of patients, surgery is performed in case of confirmation of indications by vascular surgeons.

Due to participation of T and B lymphocytes in the pathomechanism of the disease, the first biological drug which turned out to be effective in the treatment of IgG4-RD was rituximab (RTX). Typically this drug is used intravenously at a dose of 1 g every 15 days, up to a dose of 2 g [91]. In a prospective open-label clinical trial, RTX was effective in 97% of patients with IgG4-RD after 6 months of therapy despite no glucocorticoids used [80]. Also, the efficacy of RTX in patients with involvement of cerebrospinal meninges was reported on [92]. Currently RTX is recommended by experts for use as a second-line therapy in patients with recurrent disease or not responding to basic treatment [92].

So far, the data from a clinical trial with XmAB5871, i.e., a reversible inhibitor of CD19+ on B lymphocytes, were not published.

The patients with IgG4-RD are shown in **Figure 6**, before and after treatment.

#### **Figure 6.**

*Typical Mikulicz disease (IgG4-related disease) with lacrimal enlargement at the diagnosis (A, B) and after 10 months of treatment (C, D) with prednison 0.6 mg/kg/day.*

**85**

**Author details**

Agata Sebastian1

provided the original work is properly cited.

\*, Piotr Donizy2

Wroclaw Medical University, Wroclaw, Poland

Wroclaw Medical University, Wroclaw, Poland

1 Department of Rheumatology and Internal Medicine,

\*Address all correspondence to: agatasebastian@vp.pl

2 Department of Pathomorphology and Oncological Cytology,

*IgG4-Related Disease and the Spectrum of Mimics in Rheumatology*

disease is active if the index score is 3 or higher [93].

**9. Evaluation of disease activity and efficacy of the therapy**

For evaluation of disease activity and efficacy of the therapy, IgG4 Responder index is used. This index includes 25 domains, regarding organ location of lesions and general symptoms. For every domain, 0 to 3 scores may be assigned. The

The prognosis regarding IgG4-RD is not known. There are no long-term, welldesigned observational studies. It seems that spontaneous remissions rarely occur. However, the disease recurrences are frequently observed when glucocorticoids are reduced. The disease, if not diagnosed, may lead to irreversible fibrosis and damage of the involved organs. It should be remembered that due to the diversity of clinical pictures in IgG4-RD, all physicians may encounter this entity in their practice,

*DOI: http://dx.doi.org/10.5772/intechopen.83368*

regardless of their specialty.

**Conflict of interest**

None declare.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

and Piotr Wiland1
