Phagocyte dysfunctions common clinical
• Recurrent dermatological infections with bacteria and fungi such as Staphylococcus, Pseudomonas, E. cali and Aspergillus
• Subcutaneous, lymph node, lung and liver abscesses
• Frequent lung infections, abscess and pneumatocele formation contributing to chronic disease
• Frequent bone and joint infections
Chronic Granulomatosis Disease
• It shows X-linked (most common) or autosomal recessive inheritance.
pathogenesis
• There is a deficiency of NADPH oxidase.
• Bacterial killing is detective while chemotaxis, opsonization, and phagocytosis are normal. Bacteria are normally phagocytosed but cannot be killed. Bactericidal activity is impaired.
• In normal leukocytes, after phagocytosis, the hexose-monophosphate shunt is activated and oxygen production and glucose metabolism are accelerated. Subsequently, with the addition of NAD and NADP coenzymes to the hexose monophosphate shunt, hydrogen peroxide (H2O2) and superoxide formation occurs. Peroxide myeloperoxidase kills bacteria.
• The leukocytes of patients with chronic granulomatosis have abnormal or deficient NADPH oxidase. After phagocytosis, there is no increase in glucose metabolism and oxygen consumption. No superoxide or hydrogen peroxide is formed. Catalase-positive bacteria cannot be killed due to insufficient peroxide formation. Catalase-negative bacteria that peroxidize themselves normally die.
Clinic
• It manifests itself with recurrent pyogenic infections in the first years of life. Cellulite is common. Suppuration is seen in the lymph nodes from which that area drains.
• Infections with catalase-positive bacteria such as staphylococci, fungi (Aspergillus) and tuberculosis are common.
• Late-healing recurrent staphylococcal neck abscesses are the most common clinical findings. The most common cause of death in the disease is Aspergillus pneumonia in the lung.
• Perirectal abscesses, recurrent skin abscesses, folliculitis, cutaneous granuloma and discoid lupus erythematosus should suggest chronic granulomatous disease.
• Pyloric stenosis, ileal obstruction and hydronephrosis may be seen in patients due to granulomatous reaction.
• There is reactive hypergammaglobulinemia due to severe infections.
Diagnosis
• Nitroblue can be put with tetrazolium (NBT) test. Normal leukocytes show 100% NBT positivity. If 70-90% is suspicious and less than 10%, the disease should be considered.
• The NBT test is a good screening test and is widely used. A more precise diagnosis is made by flow cytometric "dihydrorhodamine 123 fluorescence test" (DHR test).
• In the second trimester of pregnancy, prenatal diagnosis can be made by NBT test in fetal blood.
• Serology is positive for Crohn's in 80% of cases.
Treatment
• Especially bactericidal antibiotics are used against the causative organism. IFN-gamma therapy is helpful. Bone marrow transplantation is the only known curative treatment.
• Gamma interferon increases superoxide anion formation in vitro and reduces the incidence of new infections. Long-term use of trimethoprim sulfamethoxazole in chronic granulomatous disease may also reduce the development of infections.
• Hemophagocytic syndrome may develop and is treated with steroid therapy and discontinuation of IFN-y therapy.
Myeloperoxidase Deficiency
• It is an oxidative metabolism disorder. This enzyme is the enzyme that converts Hp/i into more lethal hypochlorite forms. Ultimately, H p 2 mediated killing is impaired. OR passes. Catalase (+) and (-) intracellular bacteria killing is defective.
• It is usually asymptomatic. Diffuse candida infection can be seen in diabetic patients.
G6PD Deficiency
• G6PD deficiency in leukocytes causes recurrent pyogenic infections.
• Bactericidal activity is impaired.
Chediak Higashi Syndrome
• It is a rare autosomal recessive disease.
• Bactericidal activity and chemotaxis are impaired.
• It is characterized by defective neutrophil degranulation, bleeding diathesis, partial oculocutaneous albinism, and progressive peripheral neuropathy.
• It is characterized by giant cytoplasmic granulation formations stained with PAS (+) in neutrophils.
• The predominant feature in patients is light-colored hair and skin and photophobia.
• S. aureus is the most common infecting agent.
• Patients have bleeding diathesis, bleeding time is long, but platelet count is normal.
• The most important life-threatening complication is the "hemophagocytic syndrome" with pancytopenia, high fever, histiocytic infiltration of the liver, spleen and lymph nodes.
• This syndrome is most commonly activated by EBV and occurs in 85% of cases and results in death.
Treatment
• Very high dose of vitamin C improves clinical findings.
• Curative treatment is allogeneic bone marrow transplantation.
Leukocyte Adhesion Defect
• OR indicates transition.
Type 1: CD18 deficiency. β2 integrin is deficient. (β2 integrins are formed by linking a chains (CDIIa,b,c,d) with β chains (CD18)].
Type 2: CD 15 (Sialyl-Lewis X fucolization defect) is deficient.
Type 3: (There is Kindlin deficiency)
• Recurrent bacterial and opportunistic infections (with S. aureus and gr (-) enteric bacilli)
• Severe gingivitis and periodontitis
• Frequent superficial bacterial infections
• Delay in wound healing (first the navel is delayed)
• No pus is seen.
• The number of neutrophils in the peripheral blood circulation is over 30.000/mm3. It may even exceed 100,000/mm3. (E-selectin deficiency develops leukopenia, not leukocytosis).
• Fucose sugar (corrects glycosylation) is used in the treatment of type 2.