Because of the many organs that IgG4-RD can affect, the disease can exist in multiple ways associated with many symptoms. A couple of important themes occur, however:
- IgG4-RD often presents as a mass that mimics a cancer. Many patients, unfortunately, have undergone surgery to remove what was thought to be a tumor, only to learn that their true diagnosis is IgG4-RD.
- IgG4-RD is often associated with allergic symptoms (e.g., asthma, allergic rhinitis, eczema, etc.) that are not linked to IgG4-RD for years because these symptoms are so common in the general population.
IgG4-RD typically has a subacute onset, meaning many patients have had active disease with no signs or symptoms for months or even years before the diagnosis is made. The result of this subacute onset is that organ damage often occurs even while the patient is feeling well, long before he or she comes to medical attention.
Patients often feel well for long periods of time despite having disease in multiple organs. Fevers are rare to non-existent in IgG4-RD. Fatigue is often a common symptom, but because fatigue can be a common symptom for many conditions, patients often endure this symptom for long periods of time without a diagnosis. Weight loss can be a prominent component of how IgG4-RD presents. The loss of anywhere between ten and fifty pounds in IgG4-RD is often because of subclinical pancreatic dysfunction. The damaged pancreas is no longer making the appropriate amount of digestive enzymes. As a result, patients do not absorb nutrients and calories from their food and often experience extreme weight loss that defies diagnosis for an extended period of time.
To a large extent, the patient’s symptoms are dictated by the type of organ affected. The most common symptoms below are grouped according to organ:
Meninges – Patients with IgG4-RD affecting the meninges often present with headaches or dysfunction of the cranial nerves, which control eye movements, speech, swallowing, hearing, and other critical functions.
Orbits – Patients with IgG4-RD affecting the orbits, particularly the extraocular muscles (muscles controlling eyeball), frequently develop a prominence (bulging) of one or both eyes known as “proptosis”. Some patients also develop double vision and the inability to move their eyes together in a coordinated fashion because of tethering of the extra-ocular muscles.
Lacrimal glands – The lacrimal glands typically become enlarged. While they are normally not visible in healthy people, in patients with IgG4-related dacryoadenitis (lacrimal gland disease), the glands may bulge noticeably under the eyelids.
Major salivary glands – The parotid, submandibular and sublingual glands, like the lacrimal glands, often expand substantially in size, causing noticeable bulges on the sides of the face or below the chin. The overall production of saliva is also often affected, leading to symptoms of a dry mouth.
Thyroid gland – The main appearance of IgG4-RD in the thyroid gland is a non-cancerous, yet tumorous enlargement of the gland known as Riedel’s thyroiditis (“Ree duls”). Inflammation within the thyroid gland can extend through the thyroid capsule and into surrounding tissues, particularly the airway. This can sometimes lead to airway compromise, requiring major surgery to remove the invasive inflammatory tissue that originated in the thyroid.
Lungs – Patients can have symptoms of allergy and shortness of breath. The radiology features of IgG4-RD in the lung are extremely diverse and can mimic many other disorders. The lining of the chest wall, the pleura, can also be affected by IgG4-RD.
Aorta – Aortic lesions can be silent for long periods of time, until complications develop. In the thoracic aorta (small branches that supply blood to the ribs and chest), the vessel wall grows thick because of internal inflammation. The presence of IgG4-RD is occasionally detected at surgery for an aortic aneurysm. In the abdomen, inflammation caused by IgG4-RD tends to affect around the aorta, rather than involve it directly. A peri-aortic inflammation can trap nearby structures, such as the ureters (the channel urine passes from kidney to bladder), leading to the blockage of urine flow from the kidney, which is a condition known as “hydronephrosis”.
Kidneys – Kidney lesions, like those of the aorta, can also be clinically silent until advanced damage has occurred. Signs of early kidney injury, however, can be detected on routine blood tests. The kidneys often become enlarged when affected by IgG4-RD, and renal cell carcinoma (a primary kidney cancer) is occasionally misdiagnosed.
Pancreas – The classic presentation of IgG4-RD in the pancreas is painless jaundice (yellowing of the skin) that develops because inflammation in the head of the pancreas blocks the flow of bile through the common bile duct. These patients are typically mistaken early on for having pancreatic cancer. Patients with IgG4-related autoimmune pancreatitis often have abdominal pain that ranges from severe (less common) to mild or even barely noticeable. Exocrine failure of the pancreas, as noted, can lead to substantial weight loss. Endocrine failure of the pancreas can lead to diabetes mellitus.
Bile ducts – Patients with bile duct lesions also often present with painless jaundice and are often felt likely to have cholangiocarcinoma: a tumor of the bile ducts.