The presentation of IgG4-related disease (IgG4-RD) among gastroenterologists is increasing as awareness of the disease grows and as specialists become more accustomed to identifying the distinctive but rare symptoms. A chronic, multi-organ inflammatory condition, IgG4-RD was recognized only about 15 years ago as a distinct pathologic entity, receiving its designation in 2012 as “IgG4-RD” by an international multidisciplinary research panel.
“Typically the presentation is asymptotic—the patient does not arrive with distinctive symptoms or if symptoms are present, they typically mimic pancreatic cancer,” says Jorge V. Obando, MD, a Duke gastroenterologist and medical director of the gastroenterology program at Duke Raleigh Hospital.
Obando and colleagues see more IgG4-RD cases than ever, but Obando notes that a regional academic medical center such as Duke is a more likely destination for complex referrals—thus the incidence of the disease. Obando and other gastroenterologists often collaborate on cases with E. William St. Clair, MD, chief of the Duke Division of Rheumatology and Immunology, who is an expert on the condition.
A patient is typically referred to Duke after a patient presents with obstructive jaundice or after a CT scan has identified a lesion in the pancreas. “In those cases, pancreatic cancer is high on the list of potential conditions and is the key reason for referral to us,” Obando says.
Clinical suspicion is triggered when tumefactive lesions are found during physical exam or detected on radiologic imaging, St. Clair says. Elevated serum levels of IgG4 are a key diagnostic marker, but this finding may only be present in three-quarters of patients. Interpreting serum IgG4 levels presents challenges because of limits in the sensitivity and specificity of this test.
“The diagnosis of this disease usually requires clinical judgement and a tissue biopsy to reach the correct diagnosis," St. Clair says. The disease has a peak onset between ages 60 and 70. Though good epidemiologic studies are lacking, the condition has approximately the same prevalence as scleroderma.
Obando says that gastroenterologists are more attentive to IgG4-RD as a potential disease condition. “But we are still at the very beginning of our awareness of suspecting IgG4 and diagnosing the disease more frequently.”
“The disease is old, but its description as a pathologic entity is new, and we understand it better today because of its association with both elevated IgG4-levels in blood and IgG4 plasma cells in tissue,” says St. Clair.
Clinical Spectrum of IgG4-RD
- Dacryoadenitis/Sialadenitis: Mikulicz disease, Kuttner tumor, sclerosing dacryoadenitis
- Orbital: Orbital myositis, enlargement of orbital nerves, sclerosing orbital inflammation
- Pulmonary: Inflammatory pseudotumor, interstitial involvement, bronchial involvement, hilar/mediastinal lymphadenopathy, pleural thickening/effusions
- Hepatobiliary: Sclerosing cholangitis, IgG4-related hepatic disease
- Pancreas: Type 1 autoimmune pancreatitis
- Renal/Urinary Tract: Tubulointerstitial nephritis, retroperitoneal fibrosis, prostatitis
- Endocrine: Riedel’s thyroiditis, diabetes (chronic pancreatitis)
- Central Nervous System: Pachymeningitis, dural thickening, hypophysitis, intracranial lesions
- Lymphatic: IgG4-associated lymphadenopathy
- Cardiovascular: Periaortitis, coronary artery involvement
- Other: Arthritis, skin disease