For over three decades, Dr. Ben Katz and his research team have been treating patients with chronic granulomatous disease (CGD) and working to build a better understanding of the disease itself. In 2015, Dr. Katz contributed to the publication of a study in the Pediatric Infectious Disease Journal that reviewed data from 27 patients from March 1985 to November 2013. Within this large, single-center U.S. experience, the researchers offered an update to historical data on CGD, its impact, and its management.

Now, in 2022, Dr. Katz and his team expanded their study, with their data culminating in new insights into CGD. This study, published in the Journal of Clinical Immunology, followed 26 patients with CGD – five of whom are female – from November 2013 to December 2019.

Recently, Dr. Katz and I sat down to discuss what chronic granulomatous disease is, how it is treated, and what the results of this new study tell us about the treatment, management, and prognosis of CGD.

About Dr. Ben Katz, MD

After beginning his educational journey at New York University School of Medicine, Dr. Ben Katz, MD pursued postgraduate training – a residency in pediatrics at NYU Medical Center, followed by a fellowship in infectious disease at Yale University School of Medicine.

Dr. Katz is now board-certified in pediatric infectious diseases. He is a member of both the Society for Pediatric Research and the Infectious Diseases Society of America.

Currently, Dr. Katz is a Professor of Pediatrics at Northwestern University Feinberg School of Medicine, as well as Attending Physician at the Ann & Robert H. Lurie Children’s Hospital of Chicago. His clinical interests include myalgic encephalomyelitis (chronic fatigue syndrome), Epstein-Barr virus, infections in transplant recipients, respiratory syncytial virus (RSV), travel immunizations, adenovirus infections, and chronic granulomatous disease (CGD).

When I was a fellow at Yale, I trained under Dr. George Miller who had a big interest in Epstein-Barr virus. This interest really blossomed when I moved to Chicago, with my interest in RSV increasing along the way. But CGD came from starting at Lurie Children’s over 30 years ago. The director of my program at the time, Dr Shulman, had a large cohort of patients with CGD, and I ended up acquiring that interest and becoming committed to improving life for this group of patients.

Learn more about Dr. Katz here.

Chronic Granulomatous Disease (CGD): An Overview

As Dr. Katz describes:

Chronic granulomatous disease is a disease in which white blood cells can’t do their complete jobs. Think about old commercials about roach motels: the bugs could check in but not out. Normally, white blood cells engulf bacteria and kill them – the bacteria enter the cell but is killed before it can have any effect. But in people with CGD, the phagocytes – the white blood cells – don’t work correctly and can’t kill the bacteria.

Chronic granulomatous disease is considered to be a genetic primary immunodeficiency disease. CYBA, CYBB, NCF1, NCF2, or NCF4 gene mutations cause phagocyte malfunction. While CYBB gene mutations are inherited in an X-linked recessive pattern, the remaining mutations are inherited in autosomal recessive patterns. An estimated 1 in every 200,000 people are born with CGD.

People with CGD are more susceptible to fungi and bacteria, and may become very sick from illnesses that might be mild in other people. Granulomas (scars) may form at the site of infection or inflammation. While CGD is most often diagnosed in childhood, some may be diagnosed in adulthood. CGD is more common in males than females. Symptoms and characteristics can (but do not always) include:

• Fever
• Chest pain while inhaling or exhaling
• Skin, liver, lung, lymph node, and gastrointestinal infections (among others)
• Pneumonia
• Diarrhea
• Abdominal pain
• Skin irritation (swelling, rash, redness)
• Mouth swelling and redness
• A persistent runny nose
• Swollen lymph nodes

How can parents or physicians approach identification of an immunodeficiency?

Dr. Katz explains that there are certain ways in which parents or physicians can identify an immunodeficiency:

You have to think about immunodeficiency if you have any patient who gets an unusual infection or unusual germs. Certain infections are very characteristic of CGD. Many GI groups now recognize that early-onset inflammatory bowel disease should lead to an immune workup, and there are now guidelines in place which state that. Failure to thrive can also be a manifestation of primary immunodeficiency.

Early diagnosis can be crucial for patients with chronic granulomatous disease. This is because it can allow for earlier treatment and better overall outcomes. It also helps to protect patients against further damage. For example, if someone has multiple bouts of pneumonia or liver abscesses before a diagnosis is made, this person may also have organ damage that may not be reversible.

How is CGD Treated?

Decades ago, chronic granulomatous disease was initially named “fatal granulomatous disease (of childhood).” This is because CGD was often fatal by ages five to six. However, there have been numerous treatment advances since then which have helped extend overall survival rates and improve quality of life. Currently, shares Dr. Katz, treatment options include:

Antibacterial and antifungal prophylaxis, as well as interferon-gamma. Bactrim with antifungal prophylaxis is usually very helpful for children and we’ve seen a lot of children improve using this. As for interferon-gamma, an NIH trial found that interferon-gamma can reduce the infection rate in CGD by more than two-thirds. It helps to ‘jazz up’ other parts of the patient’s sick immune system, so to speak.

Unfortunately, some individuals still get infections while on prophylaxis. Dr. Katz explains that patients with CGD who are short or underweight, or have other comorbidities, are generally those who have gotten infections despite prophylaxis.

Researchers are also beginning to explore gene therapy as a potential therapeutic option for those with CGD. Currently, studies are being performed that are centered around those with X-linked CGD. More research and data will be available in the future.

Join us in Part 2 as we discuss bone marrow transplantation, research and its findings, and how families can find help.