Is Your SCIg Therapy for PI Working? How to Spot Breakthrough Infections

One of the hardest things about taking subcutaneous immunoglobulin (SCIg) for primary immunodeficiency (PI) can be knowing what “working” is supposed to look like.

But that doesn’t mean you won’t get any infections at all — or if you do, that your treatment isn’t working, says Dr. Gernez. While some anxiety is common, the key is knowing what’s normal for you and recognizing when that pattern starts to change.

Tracking IgG Numbers Is Only Part of the Picture

“With SCIg, levels are relatively steady, so we focus on the combination of the steady-state IgG level and the patient’s clinical course,” she says. The goal isn’t to simply reach a laboratory reference range, but rather to find the dose and level that adequately protect the individual, says Gernez.

Along with the IgG level, doctors consider how someone is doing over time, including the severity and frequency of infections, antibiotic use, recovery between illnesses, complications, and how much infections disrupt everyday life, she says.

Breakthrough Infections and Subtle Warning Signs

A breakthrough infection is an infection that occurs despite treatment meant to reduce infection risk, says Gernez.

“The most common misunderstanding when it comes to SCIg therapy is that ‘no infections’ is the only sign of success — or, conversely, that every cold means treatment has failed,” says Gernez.

IgG replacement is especially effective at reducing serious bacterial infections and their long-term consequences, but it can’t prevent every viral illness, fully replace mucosal immunity (immune defenses that protect moist surfaces such as the nose, airways, and digestive tract), or correct all the inflammatory and autoimmune complications of PI, says Gernez.

SCIg is made up almost entirely of IgG, and contains very little immunoglobulin A and immunoglobulin M antibodies that help protect the moist surfaces of the nose, sinuses, and airways, explains Paula Henao, MD, an immunologist at Penn State Health in Hershey, Pennsylvania, and medical director of the Immune Deficiency Foundation.

“That means colds and other respiratory viruses, sinus and ear infections, and bronchitis may still occur even when SCIg is providing good protection against more serious bacterial infections,” she says.

• Infections that are becoming more frequent, prolonged, severe, or difficult to treat
• Repeated bacterial sinus infections, bronchitis, or pneumonia
• Infections requiring repeated courses of antibiotics, intravenous (IV) antibiotics, emergency care, or hospitalization
• A persistent wet or productive cough, chronic nasal or sinus symptoms, declining exercise tolerance, or slow recovery between illnesses
• More missed work, school, exercise, or usual activities because you are sick
• Chronic diarrhea, weight loss, or signs of malabsorption, meaning your body is not properly absorbing nutrients

The site and depth of the infection is important to note, says Dr. Henao. “A deep or systemic infection such as pneumonia or sepsis says far more than a cold or a sinus infection,” she says.

Silent lung damage is the most important thing to be on the lookout for, Henao adds. "Bronchiectasis (chronic damage and widening of the airways) can progress without dramatic infections and even with a reassuring IgG level, so a persistent daily productive cough deserves evaluation even when a person otherwise feels well,” she says.

Not every change is an emergency, but certain symptoms shouldn’t wait for a routine appointment, says Gernez. “Severe breathing difficulty, hypoxia (dangerously low blood oxygen), symptoms of sepsis, or new neurologic symptoms require urgent medical attention,” she says.

How to Keep a Symptom and Infection Log

Keeping a simple health log to record infections over time can give your immunologist objective information to use when evaluating whether your infection pattern or SCIg treatment has changed, says Gernez.

Useful details to record, according to Gernez, include:

• When the illness began, where the infection occurred, your major symptoms, highest temperature, and how long you were sick
• Whether a healthcare professional confirmed the diagnosis and any cultures, tests, imaging, or other tests that were performed
• Any antibiotic or antiviral treatment, whether it worked, and whether another course was needed
• Any emergency visits, hospitalization, or use of IV antibiotics
• Work, school, exercise, or other usual activities you missed
• Whether an SCIg dose was missed, delayed, or incomplete

Henao also recommends noting roughly where you were in your infusion cycle when the infection occurred, such as soon after an infusion or shortly before the next one. “If illnesses repeatedly cluster at the same point in the cycle, that pattern can help the care team evaluate whether changing the dosing schedule might be useful,” she says.

Keep it simple, in part because you’ll be more likely to consistently update it, says Gernez. It should identify patterns and burden, but it shouldn’t feel like a full-time job, she adds.

When You May Need to Adjust Your Dose

Before increasing the dose, your doctor will confirm that the breakthrough events are true infections, and review missed or incomplete infusions, dose relative to current weight, infusion technique, and medication supply, she says.

• Weight Changes Because replacement dosing takes body weight into account, Henao says a change of more than about 5 percent is worth recalculating.
• Pregnancy Gernez says pregnancy can change immunoglobulin requirements, and Henao notes that expanding blood volume as pregnancy progresses can dilute IgG and sometimes necessitate a higher dose.
• New or Worsening Lung or Sinus Disease Bronchiectasis or chronic respiratory disease may lead doctors to aim for a higher steady-state IgG level, says Gernez.
• Gastrointestinal or Kidney Disease That Causes Protein Loss These conditions can cause immunoglobulin to leave the body more quickly and may change the dose a person needs, says Henao.
• Changes in Immune Function or Medications Developing another immune problem, such as neutropenia (a low level of infection-fighting white blood cells), or starting a medication that further suppresses the immune system can increase infection risk and prompt your care team to reassess treatment, says Gernez.