“Does IgG4-RD occur in children and, if so, is it different from the disease seen in adults?”

This GOOD QUESTION came our way recently:

“Does IgG4-RD occur in children and, if so, is it different from the disease seen in adults?”

We are grateful to Professor Omer Karadag from Haceteppe University in Ankara, Turkey, for addressing this question. Professor Karadag, an IgG4ward! Foundation Physician Network member, has led his group recently in some novel investigations of this question.

Dr. Karadag’s response:

Yes, IgG4-related disease (IgG4-RD) can happen in children, but it is much less common in the pediatric age group compared to adults.

IgG4-RD mostly affects adults, and the majority of patients are men older than 50 years of age. On the other hand, IgG4-RD is significantly less common in children. Moreover, the characteristics of the disease in children differ considerably from those in adults, particularly in terms of gender distribution. When we speak of the gender distribution in a disease, it means looking at how the disease affects males versus females. Unlike in adults, where a clear majority of the patients are male (and the male disparity grows with each passing decade of life), there is no clear gender predominance in pediatric cases. IgG4-RD is equally likely to occur in girls as it is in boys.

A second part of this question asks: “How does pediatric disease differ clinically from the disease observed in adults?”

Several important distinctions of IgG4-RD exist in children. These relate to clinical presentation, patterns of involvement, and disease course. I summarize the clinical presentation and patterns of IgG4-RD involvement in children below:

Pediatric patients with IgG4-RD tend to have involvement of superficial organs, such as:

• Salivary glands. These glands around the oral cavity (mouth) produce saliva. The typical presentation is sialadenitis (inflammation of the salivary glands), particularly affecting the parotid glands, a common feature in pediatric IgG4-RD. This can present as a painless swelling of the glands.

• Orbits and lacrimal glands. The “orbit” refers to the space within the head that contains the eye, including its nerves and muscles. Children with IgG4-RD are quite likely to present with orbital manifestations, including enlargement of the extraocular muscles (the muscles that move the eyes), and inflammation of the tear (lacrimal) glands, also known as dacryoadenitis. Either of these manifestations can lead to visible swelling around the eyes. This is more pronounced in children than in adults.

• Lymph node enlargement. The lymph nodes are part of our body’s immune system. They are normally small, bean-shaped structures situated at different sites in the body, where they serve as filters for foreign substances. The enlargement of lymph nodes is known as “lymphadenopathy.” For example, in upper respiratory infections such as Strep throat, they can be felt in the neck. Lymphadenopathy can be seen in IgG4-RD. This involvement is more commonly seen in children with IgG4-RD compared to adults. The lymph nodes can be involved alone or alongside other organ involvement in IgG4-RD.

• Pancreatic, liver, and bile duct involvement. Although less common in children than in adults, autoimmune pancreatitis can still occur in children. Children can also present with cholangitis (inflammation of the bile ducts) or involvement of the liver.

• Miscellaneous. In rare instances, children have been reported to have IgG4-RD in truly unusual places such as the large intestine, sacroiliac joints, or even in the biceps muscle.

The number of organs affected in children also appears to be different from what adults experience. Children tend to have fewer organs involved than adults at the time of diagnosis. Perhaps this is because children are watched more carefully than adults (by their parents)! But we really don’t know for certain now.

Treatment and disease course of IgG4-RD in children:

Similar to adult patients, treatment with prednisone is the first choice for this disease in children, but maintenance therapy with disease-modifying antirheumatic drugs (DMARDs) can be recommended depending on the clinical circumstances. When we say DMARDs in IgG4-RD we usually refer to methotrexate, azathioprine, and mycophenolic acid. Rituximab may also be a good alternative in therapy for refractory disease although data on these treatments in children are more limited.

IgG4-RD is a very rare entity in children, as little is known about the treatment response and disease course. Still, I am pleased to say that children generally respond well to steroids, just as adults do. The long-term course of the disease in children is variable. Since the disease is rare in this age group, we have limited information about long-term outcomes in children.

Another challenge with pediatric-onset IgG4-RD is that the disease itself is generally less known among pediatricians and can be mistaken for other conditions. On the other hand, because true IgG4-RD is rare in children, doctors must be cautious when diagnosing pediatric IgG4-RD and make sure to rule out conditions that can mimic IgG4-RD.

In a nutshell, IgG4-RD can be seen in children, with some similarities but also important differences to the disease as seen in adults. I summarize the key points here:

• IgG4-RD is a rare entity among children.

• Pediatric IgG4-RD can present in ways that differ from the usual experience of adults with this disease.

• The male predominance found in adults is not observed in pediatric cases.

• Lymphadenopathy and orbital involvement are more prominent in children, whereas pancreatic, hepatobiliary, and retroperitoneal involvements are less common than anticipated.

• Children may have a more indolent disease course and better response to treatment, but long-term outcomes are less well characterized.

To create awareness of IgG4-RD in pediatrics and to emphasize the broad clinical presentation of this disease, ongoing research and clinical observation are essential to better understand and manage this condition in the pediatric population.

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