Symptoms of chronic granulomatous disease

Patients with chronic granulomatous disease suffer from severe recurrent bacterial and fungal infections, which primarily affect organs that come into contact with the external environment (lungs, gastrointestinal tract, skin and lymph nodes draining these organs). Further, due to the hematogenous spread of the infection, other organs may suffer, most often the liver, bones, kidneys and brain.

The first symptoms in 2/3 of patients with chronic granulomatous disease appear in the first year of life (lymphadenitis, pneumonia, rectal abscesses and osteomyelitis), purulent skin lesions (sometimes from the birth) and complications from the gastrointestinal tract (vomiting as a result of obstruction of granuloma antrum department of the stomach, repeated bleeding on the background of chronic colitis), although later cases of the onset of clinical manifestations of the disease are described. A.Lun et al. Observed a woman of 43 years with a typical clinic of chronic granulomatous disease, which includes aspergillosis and the formation of intestinal granuloma, in which the first signs of the disease developed at the age of 17. A genetic examination of the patient revealed a mutation of the gp91-phox gene with nonrandomized lysing of the X chromosome.

Clinical manifestations can be very different, some children with chronic granulomatous disease may suffer from several of the complications listed above, while others may have minimal manifestations of the disease. In a number of cases, the first manifestations of chronic granulomatous disease can be mistaken for other conditions, for example, for pyloric stenosis, allergy to cow's milk protein, iron deficiency anemia. When examining children with chronic granulomatous disease, it is often possible to note a lag in physical development and anemia, especially with the X-linked variant of the disease. Children with an X-linked form of chronic granulomatous disease usually get sick earlier and are much heavier than parts with an autosomal recessive type of inheritance, especially with p47-phox deficiency.

Staphylococcus aureus, fungi of the genus Aspergillus, intestinal gram-negative flora, Burkholderia cepacia (formerly called Pseudomonas cepacia) are the most frequent pathogens causing infectious complications in CGB. Most of these germs produce catalase. Catalase destroys the hydrogen peroxide produced by the microbial life process, thus preventing the neutrophil from "borrowing" free radicals for killing. In this case, catalase-negative microorganisms, for example streptococci, die in neutrophils of patients with chronic granulomatous disease, destroyed by their own products of vital activity - hydrogen peroxide.

Fungal infections are detected in 20% of patients with chronic granulomatous disease and primarily aspergillosis.

Lung infection is the most typical infectious complication occurring in all age groups of patients with chronic granulomatous disease. These are recurrent pneumonia, damage to the basal lymph nodes, pleurisy, pleural empyema, pulmonary abscesses caused by Staphylococcus aureus, Aspergillus sp., Intestinal gram-negative bacteria {Escherichia colli, Salmonella sp., Serratia marcescens, Burkholderia cepacia).

The pathogen responsible for the development of inflammation is not always possible to identify in sputum, in connection with which, upon detection of radiological changes in the lungs, empirical antibacterial therapy is prescribed that overlaps the above-described spectrum of microorganisms. Usually this combination of aminoglycosides with ceftazidime. In the event that there is no response to empirical treatment, resort to more invasive methods of diagnosis (bronchoscopy, fine needle biopsy of the lungs, open lung biopsy). When detecting microorganisms such as Nokardia, specific antibacterial therapy is required. One of the most important causative agents of pulmonary complications in patients with chronic granulomatous disease is Burkholderia cepacia and related bacteria B. Gladioli, B. Mallei, V. Pseudomallei and V. Pickettii. These bacteria are unusually virulent in patients with chronic granulomatous disease and are one of the main causes of fatal pneumonia. Most bacteria of the genus Burkholderia are resistant to kaminoglikozidam and ceftazidime. Moreover, cultures that are plucked from sputum from patients infected with Burkholderia often grow very slowly, which allows the causative agent to proliferate in the patient's body until the development of endotoxic shock. In the event that it is possible to determine the pathogen before the dissemination of the process, the effective administration of high doses of intravenous trimethoprim-sulfamethoxazole is effective.

Cutaneous abscesses and lymphadenitis - the next most frequent occurrence of an infectious complication of chronic granulomatous disease, are most often caused by S. Aureus and Gram-negative microorganisms, including B. Cepatia and Serratia morcescens. These infections require long-term antibiotic therapy, and often also drainage for a complete cure.

Hepatic and subdiaphragmatic abscesses are also a frequent complication of chronic granulomatous disease, most often caused by S. Aureus. Patients usually develop fever, malaise, weight loss, and a decrease in appetite. Usually, there is no pain, even when palpation of the affected organ, and also often there are no laboratory disorders of the liver function. These conditions also febuyut long-term massive antibiotic therapy, in rare cases, is indicated surgical intervention.

The most serious infectious complication of chronic granulomatous disease is aspergillosis. Protocols for the treatment of aspergillosis in chronic granulomatous disease include prolonged use of amphotericin B and, if possible, removal of the aspergilloma. However, surgical treatment is not always used, because the localization of the focus in the lung, the body of the vertebrae, the ribs, and the brain excludes this method. Thus, the main method of therapy for aspergillosis in patients with chronic granulomatous disease is a long-term (4-6 months) conservative therapy with the use of amphotericin B in a dose of 1.5 mg / kg of the patient's mass and its combination with preparations of the gryazole antifungals (itraconazole, voriconazole) . In addition, it is important to establish and, if possible, eliminate the source of aspergillosis in the surrounding patient environment, because can reduce the risk of re-infection.

Osteomyelitis, pararectal abscesses are also characteristic of patients with chronic granulomatous disease and, like other infectious complications, require prolonged intensive antibacterial and antifungal therapy.

Lesions of mucous membranes include ulcerative stomatitis, gingivitis, persistent rhinitis and conjunctivitis. Enteritis and colitis, which are often found in patients with cirrhosis granulomatous disease, can be difficult to differentiate from Crohn's disease. Ament and Ochs (1973) also described perianal fistulas, vitamin B12 malabsorption and steatori. Most of these patients showed histiocytes in biopsy specimens of the mucosa of the rectus and jejunum.

In addition to infectious complications, some patients with chronic granulomatous disease have autoimmune diseases. Systemic and discoid lupus erythematosus is described both in patients with X-linked, and with autosomal recessive type of disease. Juvenile rheumatoid arthritis with a positive rheumatoid factor is described in a girl with p47 deficiency.

Patients with chronic granulomatous disease are usually less than their parents or normal siblings. The delay in physical development in such patients may be secondary in the presence of severe chronic infections (in the asymptomatic period of the disease the growth rate increases), with lesions of the gastrointestinal tract against a background of nutritional deficiency, and may also be a genetic trait of the disease, reflecting the membrane defect not only hematopoietic cells, but also other cells in patients with chronic granulomatous disease.

[1], [2], [3], [4], [5]