Chronic granulomatous disease is a rare inherited blood disorder where immune cells called phagocytes are unable to destroy bacteria, leading to recurring infections. It is caused by mutations in genes responsible for producing oxygen compounds that kill bacteria and fungi. Patients experience recurrent infections, especially of the lungs, skin, and lymph nodes. The condition is diagnosed through physical exams, laboratory tests, and imaging and is typically treated with hematopoietic stem cell transplantation, though the long-term prognosis varies depending on the specific genetic mutation.

1. CHRONIC GRANULOMATOUS DISEASE

2. What is Chronic Granulomatous Disease? A very rare inherited blood disorder where certain cells involved with immunity (phagocytes) are unable to destroy bacteria and hence the patient suffers repeated bacterial infections.

3. A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation.

4. Chronic granulomatous disease is now known to be caused by a defect in the nicotinamide adenine dinucleotide phosphate (NADPH), reduced form, oxidase enzyme complex of phagocytes. Chronic granulomatous disease refers to the characteristic granulomas that develop in response to chronic inflammation.

5. The most commonly involved organs are those that serve as barriers against the entry of microorganisms from the environment, including the skin, lungs, GI tract, lymph nodes, liver, and spleen.

6. What causes Chronic Granulomatous Disease? Patients with CGD have poorly-functioning phagocytes caused by mutations in one of four different genes. The abnormal genes cannot make proteins required for the production of oxygen byproducts, such as hydrogen peroxide and superoxide, which kill bacteria and fungi. inherited genetic defects

7. Pathogenesis:

8. Diagnosis Physical Exam (Signs) Recurrent pneumonia Lymphadenitis Skin & Hepatic Absesses Osteomyelitis Catalase (+) organism Gram (+) S. aureus Gram (-) Aspergillus spp. C. albicans

9. Laboratory: NBT being replaced now with 1,2,3 dihydrodamienflow cytometry Florecense– oxidized by H2O2

10. Imaging Studies chest radiography CT imaging valuable in the diagnosis and management of pulmonary and hepatosplenic infections.

11. GROSS MORPHOLOGY Large well circumscribed grayish white well defined non – encapsulated tumor formed of multiple coalescent nodules

12. Group of lymph nodes – Enlarged & matted together Cut surface : Show numerous areas of yellowish cheese like necrotic tissue

13. Mxcopic Morph. suppurative lesions with collections of phagocytic cells, predominantly neutrophils, with the causative bacteria or fungi and abscess formation.

14. Associated Findings Granuloma formation Inflammatory process (hallmark) Pyloric outlet obstruction Bladder obstruction Urethral obstruction Rectal fistula Intestinal granuloma

15. Treatment Hematopoietic stem cell transplantation (HSCT) Hematopoietic stem cell transplantation from a matched donor is curative although not without significant risk.

16. Prognosis There are currently no studies detailing the long term outcome of chronic granulomatous disease with modern treatment. Without treatment, children often die in the first decade of life.

17. The increased severity of X-linked CGD results in a decreased survival rate of patients, as 20% of X-link patients die of CGD-related causes by the age of 10, in contrast to an approximate age of 35 in autosomal recessive patients.

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