Chronic granulomatous disease

What is chronic granulomatous disease?

Chronic granulomatous disease is a primary immune deficiency due to functional defects in neutrophils and macrophages. It is characterised by:

1. The inability of phagocytes — cells that ingest microorganisms — to make the chemicals necessary to kill off some types of fungi and bacteria
2. The presence of granulomas, or aggregations of immune cells which cluster around sites that are inflamed or infected
3. Inflammation, even in absence of infection

The patient’s immune system is otherwise normal and the phagocytes are still capable of eliminating most pathogens.

Chronic granulomatous disease is also called chronic septic granulomatosis, Bridges–Good syndrome and Quie syndrome.

Who gets chronic granulomatous disease?

Chronic granulomatous disease is rare and is estimated to occur in approximately 1 in 250,000 to 500,000 births. Most affected individuals are male.

What causes chronic granulomatous disease?

There are five distinct genetic mutations associated with the development of chronic granulomatous disease. In 70% of cases, this mutation is X-linked and only presents in males. The other four mutations are located on different chromosomes and inherited in an autosomal recessive pattern. About 15% of these cases are female.

The disease is due to an abnormal enzyme, NADPH oxidase.

What are the signs and symptoms of chronic granulomatous disease?

Common signs and symptoms for chronic granulomatous disease include:

• Skin or bone infections involving the bacteria Serratia marcescens. Any infant testing positive for this species should be tested for chronic granulomatous disease.
• Bacterial infections due to Staphylococcus aureus, Burkholderia cepacia complex and Nocardia.
• Fungal infections, including Aspergillus species.
• Inflammation of the intestines. This occurs in 40–50% of patients with chronic granulomatous disease, and can sometimes be mistaken for Crohn disease. It responds to treatments such as systemic steroids, antibiotics and immunosuppressive therapy but not to biologics that block tumour necrosis factor alpha (TNFα).

Infants with chronic granulomatous disease present with:

• Dermatitis
• Gastrointestinal obstruction
• Colitis with resulting diarrhea
• Failure to thrive
• Recurrent infections

How is chronic granulomatous disease diagnosed?

Diagnosis of chronic granulomatous disease is based on patient’s signs and symptoms and history of specific recurrent infections.

Tests used to diagnose chronic granulomatous disease include:

• Dihydrorhodamine reduction (DHR)
• Nitroblue tetrazolium

DHR is also known as the Neutrophil Oxidative Burst Measurement test. It assesses phagocyte production of hydrogen peroxide and other important chemicals. Nitroblue tetrazolium is not considered as accurate as DHR. After diagnosis, further testing is done to establish the genetic subtype.

How is chronic granulomatous disease treated?

Chronic granulomatous disease is treated with:

• Aggressive antibiotic therapy, intravenously if necessary, and preferably with a specific rather than a broad-spectrum antibiotic
• Transfusion of plasma
• Antibiotic prophylaxis with a combination of trimethoprim and sulfamethoxazole
• Regular use of itraconazole, an oral antifungal drug
• Injections of gamma interferon 3 times weekly

Chronic granulomatous disease can be cured by bone marrow transplant but this procedure is complex and this option is not available to all patients.

What is the prognosis for patients with chronic granulomatous disease?

Due to advances in medical technology/treatment, the prognosis for chronic granulomatous disease patients has improved substantially. Many patients are able to lead full and healthy lives, with some restrictions such as:

• Swimming only in chlorinated pools
• Getting prompt treatment for minor infections
• Avoiding some outdoor activities such as raking, mulching or mowing (due to risk of Aspergillus exposure)
• Avoiding of the use of marijuana or marijuana products, due to Aspergillus exposure