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).

Following a successful induction of remission, maintenance therapy might be given in some cases, for example when there is a high risk of relapse or in patients with organ-threatening manifestations. Common maintenancy therapy is prednisolone 2.5–5 mg per day, or use of a steroid-sparing agent instead.

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.

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.

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.

Corticosteroids, typically high-dose prednisone (1 mg/kg/day), must be started as soon as the diagnosis is suspected (even before the diagnosis is confirmed by biopsy) to prevent irreversible blindness secondary to ophthalmic artery occlusion. Steroids do not prevent the diagnosis from later being confirmed by biopsy, although certain changes in the histology may be observed towards the end of the first week of treatment and are more difficult to identify after a couple of months. The dose of prednisone is lowered after 2–4 weeks, and slowly tapered over 9–12 months. Tapering may require two or more years. Oral steroids are at least as effective as intravenous steroids, except in the treatment of acute visual loss where intravenous steroids appear to offer significant benefit over oral steroids. It is unclear if adding a small amount of aspirin is beneficial or not as it has not been studied.

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.

Ligneous conjunctivitis may be managed by topical treatments of plasminogen, topical and subconjunctival fresh frozen plasma, and fibrinolytic therapy.

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.

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.

Although orbital cellulitis is considered an ophthalmic emergency the prognosis is good if prompt medical treatment is received.

Small extramacular lesions (lesions not threatening vision) may be observed without treatment. Sight-threatening lesions are treated for 4–6 weeks with triple therapy consisting of pyrimethamine, sulfadiazine, and folinic acid. During treatment with pyrimethamine, leukocyte and platelet counts should be monitored weekly. Folinic acid protects against the decrease in platelets and white blood cells induced by pyrimethamine.

Prednisone may be used for 3–6 weeks to reduce macular or optic nerve inflammation and can be started on day 3 of antibiotic therapy. Corticosteroids should not be used without concurrent antibiotic treatment or in immunocompromised patients due to the risk of exacerbation of the disease. Currently, there is no published evidence from randomized controlled trials demonstrating that corticosteroids would be an effective adjunct for treating ocular toxoplasmosis.

Trimethoprim-Sulfamethoxazole has been shown to be equivalent to triple therapy in the treatment of ocular toxoplasmosis and may be better tolerated. Clindamycin and azithromycin can also be considered as alternative therapies. Spiramycin may be used safely without undue risk of teratogenicity and may reduce the rate of transmission to the fetus.

AIDS patients require chronic maintenance treatment.

IgG4-related disease responds well, and often dramatically, to glucocorticoid therapy, provided that advanced fibrotic lesions have not resulted in irreversible damage, and this has included resolution of radiologic findings. Men given glucocorticoids to treat IgG4-related disease at other anatomical sites sometimes report relief of their lower urinary tract symptoms, suggesting that IgG4-related prostatitis may be underdiagnosed.

Cases are however likely to get misdiagnosed as benign prostatic hyperplasia and to get treated alternatively with medications such as alpha blockers. The efficacy of alpha blockers in IgG4-related prostatitis remains unclear.

Immediate treatment is very important for someone with orbital cellulitis. Treatment typically involves intravenous (IV) antibiotics in the hospital and frequent observation (every 4–6 hours). Along with this several laboratory tests are run including a complete blood count, differential, and blood culture.

- Antibiotic therapy – Since orbital cellulitis is commonly caused by "Staphylococcus" and "Streptococcus" species both penicillins and cephalosporins are typically the best choices for IV antibiotics. However, due to the increasing rise of MRSA (methicillin-resistant "Staphylococcus aureus") orbital cellulitis can also be treated with Vancomycin, Clindamycin, or Doxycycline. If improvement is noted after 48 hours of IV antibiotics, healthcare professions can then consider switching a patient to oral antibiotics (which must be used for 2–3 weeks).

- Surgical intervention – An abscess can threaten the vision or neurological status of a patient with orbital cellulitis, therefore sometimes surgical intervention is necessary. Surgery typically requires drainage of the sinuses and if a subperiosteal abscess is present in the medial orbit, drainage can be performed endoscopically. Post-operatively, patients must follow up regularly with their surgeon and remain under close observation.

In terms of the treatment of cytomegalovirus retinitis, oral valganciclovir, intravenous ganciclovir, IV foscarnet, and IV cidofovir are all efficient in the treatment of this condition. Also intravitreal injections, an injection of medicine into the vitreous near the retina, of foscarnet in concomitance with oral valganciclovir can be used for treatment as well.

Often individuals with CMV retinitis will need surgery for either retinal detachment or intravitreal instillation of ganciclovir. Retinal detachment occurs in up to 29% of affected eyes, repair being most effective with endolaser and silicone oil endotamponade.Intravitreal ganciclovir implant has the benefit of less systemic toxicity. An adverse effect of this is retinal detachment (and vitreous hemorrhage), also there is no systemic beneficial effect for cytomegalovirus organ disease.

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

IgG4-related ophthalmic disease (IgG4-ROD) is the recommended term to describe orbital (eye socket) manifestations of the systemic condition IgG4-related disease, which is characterised by infiltration of lymphocytes and plasma cells and subsequent fibrosis in involved structures. It can involve one or more of the orbital structures.

Frequently involved structures include the lacrimal glands, extraocular muscles, infraorbital nerve, supraorbital nerve and eyelids. It has also been speculated that ligneous conjunctivitis may be a manifestation of IgG4-related disease (IgG4-RD).

As is the case with other manifestations of IgG4-related disease, a prompt response to steroid therapy is a characteristic feature of IgG4-ROD in most cases, unless significant fibrosis has already occurred.

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

Riedel's thyroiditis is characterized by a replacement of the normal thyroid parenchyma by a dense fibrosis that invades adjacent structures of the neck and extends beyond the thyroid capsule. This makes the thyroid gland stone-hard (woody) and fixed to adjacent structures. The inflammatory process infiltrates muscles and causes symptoms of tracheal compression. Surgical treatment is required to relieve tracheal or esophageal obstruction.

Symptoms, if any, can be mild even in the presence of significant swelling or masses.

Lacrimal gland involvement may cause swelling of the upper eyelid, or proptosis if there is severe swelling. Other orbital masses or inflammation can result in visual disturbance (blurred vision, double vision, visual field impairment), restricted eye movements, pain or discomfort, numbness in the distribution of the supraorbital and/or infraorbital nerves, or proptosis.

IgG4-related ophthalmic disease has been estimated to account for approximately 25% of all cases of proptosis, eyelid swelling and other features of orbital swelling.

Idiopathic orbital inflammatory (IOI) disease, or orbital pseudotumor, refers to a marginated mass-like enhancing soft tissue involving any area of the orbit. It is the most common painful orbital mass in the adult population, and is associated with proptosis, cranial nerve (Tolosa–Hunt syndrome), uveitis, and retinal detachment. Idiopathic orbital inflammatory syndrome, also known as orbital pseudotumor, was first described by Gleason in 1903 and by Busse and Hochhmein. It was then characterized as a distinct entity in 1905 by Birch-Hirschfeld. It is a benign, nongranulomatous orbital inflammatory process characterized by extraocular orbital and adnexal inflammation with no known local or systemic cause. Its diagnosis is of exclusion once neoplasm, primary infection and systemic disorders have been ruled-out. Once diagnosed, it is characterized by its chronicity, anatomic location or histologic subtype.

Idiopathic orbital inflammation has a varied clinical presentation depending on the involved tissue. It can range from a diffuse inflammatory process to a more localized inflammation of muscle, lacrimal gland or orbital fat. Its former name, orbital pseudotumor, is derived due to resemblance to a neoplasm. However, histologically it is characterized by inflammation. Although a benign condition, it may present with an aggressive clinical course with severe vision loss and oculomotor dysfunction.

If the diagnostic workup reveals a systemic disease process, directed therapies to treat that underlying cause should be initiated. If the amaurosis fugax is caused by an atherosclerotic lesion, aspirin is indicated, and a carotid endarterectomy considered based on the location and grade of the stenosis. Generally, if the carotid artery is still patent, the greater the stenosis, the greater the indication for endarterectomy. "Amaurosis fugax appears to be a particularly favorable indication for carotid endarterectomy. Left untreated, this event carries a high risk of stroke; after carotid endarterectomy, which has a low operative risk, there is a very low postoperative stroke rate." However, the rate of subsequent stroke after amaurosis is significantly less than after a hemispheric TIA, therefore there remains debate as to the precise indications for which a carotid endarterectomy should be performed. If the full diagnostic workup is completely normal, patient observation is recommended.

Retinal vasculitis is inflammation of the vascular branches of the retinal artery, caused either by primary ocular disease processes, or as a specific presentation of any systemic form of vasculitis such as Behçet's disease, sarcoidosis, multiple sclerosis, or any form of systemic nectrozing vasculitis such as temporal arteritis, polyarteritis nodosa, and granulomatosis with polyangiitis, or due to lupus erythematosus, or rheumatoid arthritis. Eales disease, pars planitis, birdshot retinochoroidopathy (autoimmune bilateral posterior uveitis), and Fuchs heterochromic iridocyclitis (FHI) can also cause retinal vasculitis. Infectious pathogens such as "Mycobacterium tuberculosis", visceral larva migrans ("Toxocara canis" & "Toxocara cati") can also cause retinal vasculitis.

Associated visual loss rarely recovers and may even progress after the drug is discontinued.

Idiopathic granulomatous mastitis is defined as granulomatous mastits without any other attributable cause such as those above mentioned. It occurs on average two years and almost exclusively up to six years after pregnancy, usual age range is 17 to 42 years. Some cases have been reported that were related to drug induced hyperprolactinemia.

Exceptionally rarely it has been diagnosed during pregnancy and in men.