Yael Gernez, MD, PhD, is a pediatric allergy and immunology specialist at Stanford Children's Health in California.
Primary immunodeficiency diseases (PIDDs) are a group of more than 550 conditions in which your immune system doesn't work the way it should. Your body's defenses have a harder time protecting you from germs, which can cause infections that make you sick.
Gene changes that are passed from parent to child cause many types of PIDDs. Symptoms often start when you're a baby or a child, but sometimes they don't show up until you're an adult. Treatment options can include medicines to boost your immune system, drugs to prevent or treat infections, stem cell transplants, and gene therapy. We spoke with Yael Gernez about symptoms to be aware of, vaccine safety, treatment side effects, and reasons to stay optimistic.
Q: What's one of the top questions or concerns people with PIDDs ask about?
Gernez: A question I hear very often is: "Will I still be able to live a normal life?" Many want to know how to stay safe from infections without feeling overly restricted in their daily activities.
Patients often wonder whether their treatments are working well enough, how to recognize when an infection is serious enough to call their doctor, and how to plan things like travel, school, or social events safely.
Many patients are also interested in the long-term outlook – whether their condition will improve, stay the same, or worsen over time – and what new treatments may become available.
Q: When you're living with a PIDD, what symptoms should tell you it's time to call your doctor?
Gernez: You should call your doctor or schedule an appointment with urgent care if you develop a fever, especially one above 100.4 degrees F, since this can signal an infection that needs prompt treatment.
Other warning signs include difficulty breathing, a cough that is getting worse or producing thick or discolored mucus, a severe headache or stiff neck, unusual fatigue or weakness, or diarrhea with weight loss. You should also contact your doctor if an infection isn't improving after a few days of treatment.
For people with primary immunodeficiency, infections can sometimes progress quickly, so it's important to contact your doctor early if something doesn't seem right. When in doubt, it's always safer to check in sooner rather than wait.
Q: Once you get treatment for a new infection, what can you do at home to help speed your recovery?
Gernez: One of the most important things patients can do is give their body time to recover. Rest is very important, because your body needs energy to fight an infection. Try not to rush back to normal activities too quickly. Stay well hydrated by drinking plenty of fluids. And take antibiotics exactly as prescribed – even if you start feeling better before finishing the full course.
Wearing masks and practicing good hand hygiene can help prevent spreading an infection or getting sick again. Keeping follow-up appointments is also important, so your doctor can confirm the infection has cleared. If you receive immunoglobulin replacement therapy, staying on your regular schedule can help prevent future infections.
Q: Speaking of preventing infections, what should you know about vaccines?
Gernez: Vaccines remain an important part of staying healthy, but people with PIDDs need individualized guidance.
The main distinction is between inactivated vaccines and live vaccines. Inactivated vaccines – such as flu shots, pneumococcal vaccines, COVID-19 vaccines, and tetanus boosters – are generally safe and recommended, although they may not always produce as strong an immune response.
Live vaccines – such as measles-mumps-rubella (MMR), chickenpox, or the nasal flu vaccine – may not be safe for certain patients with severe immune deficiencies. An immunologist can help determine which vaccines are appropriate.
It's also important for family members and close contacts to stay up to date on vaccines to help protect the patient.
Q: What are some common challenges for people who take medications to manage their PIDDs?
Gernez: One of the biggest challenges is the time commitment that comes with ongoing treatment. People receiving immunoglobulin therapy may need monthly intravenous infusions at an infusion center or regular injections at home.
Managing primary immunodeficiency often means balancing treatment with everyday life. Scheduling treatments around work, school, and family life can sometimes be difficult.
Some people also struggle with the emotional side of living with a chronic condition. Others may have difficulty remembering daily medications or managing side effects. Cost can also be a concern for some families, especially for therapies like immunoglobulin.
Q. What are some common side effects of long-term antibiotics or immunoglobulin? And how can you manage them?
Gernez: Long-term antibiotics can sometimes cause stomach upset, diarrhea, or yeast infections. Taking antibiotics with food may help reduce stomach irritation, and your doctor will monitor you to make sure the medication remains safe and effective over time.
Immunoglobulin therapy can occasionally cause headaches, fatigue, chills, or nausea during or shortly after intravenous infusions. Most side effects from it are mild and manageable.
Adjusting the infusion rate or taking medications such as acetaminophen beforehand can help. Subcutaneous immunoglobulin often causes fewer whole-body symptoms, but it may cause redness or swelling at the injection site, which usually improves with time.
Serious side effects are rare but are monitored closely by the medical team.
Q: Who's a good candidate for a stem cell transplant or gene therapy?
Gernez: Stem cell transplant and gene therapy are typically used for the most severe forms of primary immunodeficiency, particularly conditions such as severe combined immunodeficiency (SCID) and a few other life-threatening disorders.
These treatments are most successful when the condition is diagnosed early, before significant infections or organ damage develop.
For some of the most severe immune disorders, a stem cell transplant or gene therapy can actually correct the underlying problem. However, many people with PIDD do very well with treatments such as immunoglobulin replacement and preventive antibiotics, and never need these more intensive therapies.
Q: Along with an immunologist, what other health care professionals can be helpful to have on your medical team?
Gernez: Care for primary immunodeficiency often involves a team of specialists. In addition to an immunologist, patients may see a pulmonologist if they have lung problems from recurrent infections, or a gastroenterologist if they have digestive symptoms.
An infectious disease specialist may help manage complicated infections, and a hematologist may be involved if blood-related problems occur.
Genetic counselors can help families understand inheritance patterns, while psychologists or psychiatrists may provide support for the emotional impact of living with a chronic illness. Nurses and pharmacists also play an important role in helping patients manage treatments safely.
Q. What steps can you take if your condition makes you feel depressed?
Gernez:Mental health is an important part of overall health for people with chronic medical conditions. Studies suggest that people living with primary immunodeficiency may have higher rates of depression and anxiety. This may be related both to the immune condition itself and to the challenges of managing a chronic illness.
If you're feeling depressed, talk with your immunologist or primary care doctor. They can screen for depression and help connect you with a mental health professional. Therapy, counseling, and sometimes medication can be very effective.
Support groups for people with PIDD can also be valuable, because they connect patients with others who understand what they're going through.
If you ever have thoughts of harming yourself, seek help right away by calling 988, the Suicide and Crisis Lifeline, or going to the nearest emergency room.
Q: If you're a parent and you learn your child has a PIDD, what are some reasons to be optimistic?
Gernez: Learning that your child has a primary immunodeficiency can feel overwhelming at first. The reassuring news is that many children with PIDDs can live full and active lives with the right treatment and care.
Advances in therapies – including immunoglobulin replacement, antibiotics, gene therapy, and stem cell transplant – have greatly improved outcomes. With appropriate treatment and medical care, many children with PIDD can grow up to live very active, healthy lives.
Early diagnosis and close follow-up with an experienced immunology team are key. Parents should also know they are not alone: There are patient organizations and support networks that can help families navigate the journey.