IgG4 Related Disease

Clinical manifestations

Eye and eyelid disease. Inflammation of the eye drainage tunnels or lacrimal ducts is called dacryoadenitis. This, ocular and orbital inflammatory disease is commonly seen in people with IgG4-related eye disease. It can involve the tear producing or lacrimal gland (IgG4-related dacryoadenitis). Eye disease is present in approximately 20 percent of patients with IgG4-RD. Bilateral involvement is typical, even though the onset of clinical disease in the two glands may occur at different times. Concurrent saliva (salivary) gland involvement is common, and manifestations in organs outside of the eye are seen in approximately 70 to 80 percent of the patients concurrently. IgG4-RD appears to account for 25 to 50 percent of orbital pseudotumors, including those originally diagnosed before recognition of IgG4-RD as "idiopathic orbital inflammation" or "orbital benign lymphoid hyperplasia." Depending upon the diagnostic criteria used, IgG4-RD accounts for between approximately 5 and 25 percent of cases originally diagnosed as nongranulomatous idiopathic orbital inflammation. IgG4-RD is also recognized as a cause of orbital myositis (IgG4-related orbital myositis), and it is orbital myositis that leads most often to proptosis among patients with this disease. Histologic and serologic findings are similar to those seen in patients with sialadenitis and in other tissues. Storiform fibrosis is not a consistent finding among different studies, and it seems to be more pronounced in samples obtained from dacryoadenitis rather than from orbital pseudotumors. It is not certain whether IgG4-RD predisposes to the development of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas or other lymphomas. Several such cases have been reported, but additional studies are required. One study has indicated that a history of malignancy may itself be a risk factor for the development of IgG4-RD, rather than the converse. On the other hand, a meta-analysis of 10 studies found that the standardized incidence ratio (SIR) for lymphoma in IgG4-RD patients was higher in patients with IgG4-RD compared with the general population.[1]

Diagnosis

Biopsy shows storiform histiocytes. Storiform = whorled. "The name "storiform" originates from Latin storea (woven), as storiform tissue tends to resemble woven fabric on microscopy." [2] HIstiocytes are a type of white cell called a macrophage.
LabCertain tests are useful as part of the initial diagnostic evaluation. None of these tests alone has high diagnostic specificity, but the combination of elevations of serum IgG4, IgG1, and IgE in addition to hypocomplementemia of C3 and C4 should heighten concern for this diagnosis. The diagnosis of IgG4-RD requires the identification of characteristic findings upon biopsy of affected tissue. [3]

• IgG4
• IgE
• ESR, CRP
• C3,C4 might be low especially in patients with renal disease from IgG4RD

Treatment

• Prednisone. Most patients require treatment with  prednisone  at a dose of 0.6 mg/kg (typically 30 to 40 mg) once daily. Nearly all patients demonstrate a response to prednisone 40 mg daily within two to four weeks; many patients respond even earlier. Once a significant response is clinically evident in the affected organ system, taper the glucocorticoids gradually with a planned reduction over a two-month period and the goal of discontinuing the medication entirely. Consider methylprednisolone rather than prednisone or prednisolone in patients in whom liver disease may be present. A typical response occurs within several weeks of starting glucocorticoids meaning symptomatic improvement, reductions in the size of masses or organ enlargement, improvement in organ function, and decrease in serum concentrations of IgG4. Some patients require a few months to respond, and there are some patients who relapse and others who respond less well or not at all initially. American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR; formerly known as European League Against Rheumatism) classification criteria for IgG4-RD have "failure to respond to an appropriate glucocorticoid dose" as an exclusion criterion for classification purposes. In patients whose disease is largely fibrotic at the start of glucocorticoid therapy (eg, some patients with retroperitoneal fibrosis), responses to treatment are sometimes difficult to detect. Disease worsening while on glucocorticoid therapy, however, certainly implies another diagnosis.[4]
• Rituximab 1 gram every 15 days x2 
• Azathioprine
• Mycophenolate