Standard, and most effective, therapy to date is glandular sialadenectomy, which is associated with fairly low operative morbidity; however, in recent times, the administration of steroid (which can shrink the inflammatory lesion and is known to reduce serum IgG4 values) has been considered favorably, and may be useful in younger patients or those who refuse surgery.

As the number of published cases of AIP has increased, efforts have been focused on defining AIP as a distinct clinical and pathologic entity and toward developing some generally agreed upon diagnostic criteria and nomenclature. Terms frequently encountered are autoimmune or autoimmune-related pancreatitis, lymphoplasmacytic sclerosing pancreatitis, idiopathic tumefactive chronic pancreatitis, idiopathic pancreatitis with focal irregular narrowing of the main pancreatic duct, and non-alcoholic duct destructive chronic pancreatitis. There are also a large number of case reports employing descriptive terminology such as pancreatitis associated with Sjögren’s syndrome, primary sclerosing cholangitis, or inflammatory bowel disease. Some of the earliest cases were reported as pancreatic pseudotumor or pseudolymphoma.

AIP often completely resolves with steroid treatment. The failure to differentiate AIP from malignancy may lead to unnecessary pancreatic resection, and the characteristic lymphoplasmacytic infiltrate of AIP has been found in up to 23% of patients undergoing pancreatic resection for suspected malignancy who are ultimately found to have benign disease. In this subset of patients, a trial of steroid therapy may have prevented a Whipple procedure or complete pancreatectomy for a benign disease which responds well to medical therapy. "This benign disease resembles pancreatic carcinoma both clinically and radiographically. The diagnosis of autoimmune pancreatitis is challenging to make. However, accurate and timely diagnosis may preempt the misdiagnosis of cancer and decrease the number of unnecessary pancreatic resections." Autoimmune pancreatitis responds dramatically to corticosteroid treatment.

If relapse occurs after corticosteroid treatment or corticosteroid treatment is not tolerated, immunomodulators may be used. Immunomodulators such as azathioprine, and 6-mercaptopurine have been shown to extend remission of autoimmune pancreatitis after corticosteroid treatment. If corticosteroid and immunomodulator treatments are not sufficient, rituximab may also be used. Rituximab has been shown to induce and maintain remission.

The goal of treatment is the induction and maintenance of remission so as to prevent progression of fibrosis and organ destruction in affected organ(s).

An international panel of experts have developed recommendations for the management of IgG4-RD. They concluded that in all cases of symptomatic, active IgG4-RD that treatment is required. Some cases with asymptomatic IgG4-RD also require treatment, as some organs tend to not cause symptoms until the late stages of disease. Urgent treatment is advised with certain organ manifestations, such as aortitis, retroperitoneal fibrosis, proximal biliary strictures, tubulointerstitial nephritis, pachymeningitis, pancreatic enlargement and pericarditis.

Treatment usually consists of observation unless the patient has concern, there is pain, drainage, or other symptoms related to the lesion. Surgical removal of the affected gland would be recommended in those cases. Another treatment option would be aspiration, which can be repeated multiple times. This is commonly performed in those who are debilitated or in those whose benefit from surgery would be outweighed by the risks. Prognosis is usually good; rarely this condition may devolve into lymphoma, or could actually represent 'occult' lymphoma from the outset.

Chronic sclerosing sialadenitis is a chronic (long-lasting) inflammatory condition affecting the salivary gland. Relatively rare in occurrence, this condition is benign, but presents as hard, indurated and enlarged masses that are clinically indistinguishable from salivary gland neoplasms or tumors. It is now regarded as a manifestation of IgG4-related disease.

Involvement of the submandibular glands is also known as Küttner's tumor, named after Hermann Küttner (1870–1932), a German Oral and Maxillofacial Surgeon, who reported four cases of submandibular gland lesions for the first time in 1896.

In untreated patients with active disease, the recommended first-line agent for induction of remission is glucocorticoids unless contraindications exist. Glucocorticoids characteristically result in a rapid and often dramatic improvement in clinical features and often a resolution of radiographic features. However, where advanced fibrotic lesions have resulted in irreversible damage, the response to glucocorticoids and other current treatment options may be poor or even absent.

Although not validated yet in clinical trials, the common induction regime is prednisolone 30–40 mg per day for 2–4 weeks, then gradually tapered over 3 to 6 months. Recurrences during or after tapering of glucocorticoids are frequent however. Steroid-sparing immunosuppressive agents might be considered, depending on local availability of these drugs, for use in combination with glucocorticoids from the start of treatment. Steroid-sparing agents that have been used include rituximab, azathioprine, methotrexate, and cyclophosphamide, although trials are needed to ascertain the effectiveness of each drug in IgG4-RD.

In terms of possible treatment for the condition of idiopathic sclerosing mesenteritis, medications such as corticosteroids, tamoxifen and thalidomide have been used.

Multifocal fibrosclerosis and idiopathic fibrosclerosis are disorders of unknown aetiology, characterised by fibrous lesions (co-)occurring at a variety of sites. Known manifestations include retroperitoneal fibrosis, mediastinal fibrosis and Riedel's thyroiditis.

They are now considered to be manifestations of IgG4-related disease.

Therapy usually consists of prednisolone, nonetheless some cases may require surgery. Tamoxifen has been proposed as part of a treatment plan.

Treatment is directed to surgical relief of compressive symptoms. Tamoxifen may also be beneficial.

-Harrison's principle of internal medicine, 17th

The type of surgery which is indicated here is isthmectomy.

Although there is no curative treatment, several clinical trials are underway that aim to slow progression of this liver disease. Obeticholic acid is being investigated as a possible treatment for PSC due to its antifibrotic effects. Simtuzumab is a monoclonal antibody against the pro-fibrotic enzyme LOXL2 that is being developed as a possible therapy for PSC.

Corticosteroids remain the main treatment modality for IOI. There is usually a dramatic response to this treatment and is often viewed as pathognomonic for this disease. Although response is usually quick, many agree that corticosteroids should be continued on a tapering basis to avoid breakthrough inflammation.

Although many respond to corticosteroid treatment alone, there are several cases in which adjuvant therapy is needed. While many alternatives are available, there is no particular well-established protocol to guide adjuvant therapy. Among the available options there is: surgery, alternative corticosteroid delivery, radiation therapy, non-steroidal anti-inflammatory drugs, cytotoxic agents (chlorambucil, cyclophosphamide), corticosteroid sparing immunosuppressants (methotrexate, cyclosporine, azathioprine), IV immune-globin, plasmapheresis, and biologic treatments (such as TNF-α inhibitors).

The epidemiology of Idiopathic sclerosing mesenteritis disease is extremely rare and has only been diagnosed in about an estimated 300 patients worldwide to date (as of 2014), it is probably under diagnosed.

It can occur in children.

Benign lymphoepithelial lesion is a type of benign enlargement of the parotid and/or lacrimal glands. This pathologic state is sometimes, but not always, associated with Sjögren's syndrome.

Riedel's thyroiditis is classified as rare. Most patients remain euthyroid, but approximately 30% of patients become hypothyroid and very few patients are hyperthyroid. It is most seen in women.

No pharmacologic treatment has been approved by the U.S. Food and Drug Administration for PSC. Some experts recommend a trial of ursodeoxycholic acid (UDCA), a bile acid occurring naturally in small quantities in humans, as it has been shown to lower elevated liver enzyme numbers in patients with PSC and has proven effective in other cholestatic liver diseases. However, UDCA has yet to be shown to clearly lead to improved liver histology and survival. Guidelines from the American Association for the Study of Liver Diseases and the American College of Gastroenterology do not support the use of UDCA but guidelines from the European Association for the Study of the Liver do endorse the use of moderate doses (13-15 milligrams per kilogram) of UDCA for PSC.

Supportive treatment for PSC symptoms is the cornerstone of management. These therapies are aimed at relieving symptoms such as itching with antipruritics (e.g. bile acid sequestrants such as (cholestyramine)); antibiotics to treat episodes of acute cholangitis; and vitamin supplements, as people with PSC are often deficient in fat-soluble vitamins (vitamin A, vitamin D, vitamin E, and vitamin K).

ERCP and specialized techniques may also be needed to help distinguish between a benign PSC stricture and a bile duct cancer (cholangiocarcinoma).

Liver transplantation is the only proven long-term treatment of PSC, although only a fraction of individuals with PSC will need it. Indications for transplantation include recurrent bacterial cholangitis, decompensated cirrhosis, hepatocellular carcinoma, hilar cholangiocarcinoma, and complications of portal hypertension. Not all patients are candidates for liver transplantation, and some will experience disease recurrence afterward.

IOI or orbital pseudotumor is the second most common cause of exophthalmos following Grave’s orbitopathy and the third most common orbital disorder following thyroid orbitopathy and lymphoproliferative disease accounting for 5–17.6% of orbital disorders, There is no age, sex, or race predilection, but it is most frequently seen in middle-aged individuals. Pediatric cases account for about 17% of all cases of IOI.

Treatment protocol is not well established. Some sources report that approximately half of the patients will fully recover after lengthy (mean time 14.5 months, range 2–24 months) expectant management.

Treatment with steroids is lengthy and usually requires about 6 months. While some source report very good success with steroids most report a considerable risk of recurrence after a treatment with steroids alone. Steroids are known to cause elevation of prolactin levels and increase risk of several conditions such as diabetes, and other endocrinopathies which in turn increase the risk of IGM. Treatment with topical steroids to limit side effects was also reported in one case. For surgical treatment recurrence rates of 5-50% have been reported.

A 1997 literature review article recommended complete resection or corticosteroid therapy, stating also that long-term follow-up was indicated due to a high rate of recurrence.

Treatment with a combination of glucocorticoids and prolactin lowering medications such as bromocriptine or cabergoline was used with good success in Germany. Prolactin lowering medication has also been reported to reduce the risk of recurrence. In cases of drug-induced hyperprolactinemia (such as antipsychotics) prolactin-sparing medication can be tried.

Methotrexate alone or in combination with steroids has been used with good success. Its principal mechanism of action is immunomodulating activity, with a side effect profile that is more favorable for treating IGM.

Colchicine, azathioprine and NSAIDs have also been used.

The condition is usually self-limiting, and thus not indicated for surgery.

Treatment is directed largely to removing the cause, or, where that is impossible, to modifying its effects. Thus, therapy aimed at improving right heart function will also improve congestive hepatopathy. True nutmeg liver is usually secondary to left-sided heart failure causing congestive right heart failure, so treatment options are limited.

Plasma cell granuloma is a lesional pattern of inflammatory pseudotumour, different from the "inflammatory myofibroblastic tumor" pattern.

It is linked to IgG4-related disease.

Surgery to treat chronic pancreatitis tends to be divided into two areas – resectional and drainage procedures. Among the reasons to opt for surgery are if there is a pseudocyst, fistula, ascites, or a fixed obstruction.

Follicular hyperplasia (or "reactive follicular hyperplasia" or "lymphoid nodular hyperplasia") is a type of lymphoid hyperplasia. It is caused by a stimulation of the B cell compartment. It is caused by an abnormal proliferation of secondary follicles and occurs principally in the cortex without broaching the lymph node capsule. The follicles are cytologically polymorphous, are often polarized, and vary in size and shape. Follicular hyperplasia is distinguished from follicular lymphoma in its polyclonality and lack of bcl-2 protein expression, whereas follicular lymphoma is monoclonal, and does express bcl-2).

Pancreatic enzyme replacement is often effective in treating the malabsorption and steatorrhea associated with chronic pancreatitis. Treatment of CP consists of administration of a solution of pancreatic enzymes with meals. Some patients do have pain reduction with enzyme replacement and since they are relatively safe, giving enzyme replacement to a chronic pancreatitis patient is an acceptable step in treatment for most patients. Treatment may be more likely to be successful in those without involvement of large ducts and those with idiopathic pancreatitis.

Some specific reactive lymphadenopathies with a predominantly follicular pattern:

- Rheumatoid arthritis

- Sjogren syndrome

- IgG4-related disease (IgG4-related lymphadenopathy)

- Kimura disease

- Toxoplasmosis

- Syphilis

- Castleman disease

- HIV-associated lymphadenopathy

- Progressive transformation of germinal centers (PTGC)