Treatment of chronic granulomatous disease

Treatment of patients with chronic granulomatous disease includes:

• Prevention of infections by immunization and exclusion of contacts with possible sources of infection.
• Prophylactic continuous use of trimethoprim-sulfamethoxazole at a dose of 5 mg / kg per day for trimethoprim and antifungals (itraconazole 200 mg / day per os, but not more than 400 mg / day).
• As early as possible, swings antibacterial and antifungal therapy parenterally in high doses in the event of infectious complications. The duration of therapy depends on the severity of the disease and can range from several weeks (with purulent lymphadenitis) to several months (with liver abscesses).

In the case of aspergillosis, long-term therapy with amphotericin (preferably liposomal) was used at a dose of 1-1.5 mg / kg per day. However, the frequency of resistance of aspergillosis to amphotericin remains high, in addition, its safety profile is limiting for the use of the drug. Therefore, in recent years, new antifungal drugs have become more widespread, which have shown their activity and numerous clinical studies in various groups of immunocompromised patients with systemic mycoses - voriconazole (from the group of new azoles) and caspofungin (from the group of echinocandins). In some cases, combined therapy with both drugs is recommended (for example, in the manifestation of a fungal infection after TSCC).

In nocardia ( Nocardia asteroides ) - high doses of TMP / SMC, with ineffectiveness - minocycline or amikacin + UTI. Nocardia brasiliensis - AMK / KL or amikacin + ceftriaxone.

4. Surgical treatment in the occurrence of superficial abscesses (purulent lymphadenitis) - the application of this method is significantly limited. With liver and lung abscesses, in most cases, conservative treatment with high doses of antibiotics and antifungal drugs is effective, and operative dissection is often accompanied by suppuration of the postoperative wound and the formation of new foci. In this case, puncture drainage of the abscess under ultrasound control is possible.
5. The use of granulocyte mass obtained from donors stimulated by G-CSF.
6. The use of high doses of g-interferon (adult dose of 50 mcg / m ² n / c 3 times a week, for children: for body surface area <0.5 m ² -1.5 mcg / kg p / c 3 times a week, with a body surface area> 0.5 m ² -50 mcg / m ² n / c 3 times a week) in some patients reduces the frequency and severity of infectious manifestations.
7. When forming the obturating granulomas - glucocorticoids together with antibacterial therapy.

Bone Marrow Transplantation / Hematopoietic Stem Cells

Earlier bone marrow transplantation (TCM) or hematopoietic stem cells (TSCC) in patients with chronic granulomatous disease was accompanied by a rather high failure rate. And often this was due to the unsatisfactory pre-transplant status of patients, in particular, with fungal infection, which, as is known, along with GVHD, occupies one of the leading places in the structure of post-transplant mortality. However, recently, thanks to the expansion of the arsenal of effective antifungal drugs and the reduction in the incidence of fatal mycoses, as well as due to the development of TSCC proper technology (for example, new organ preserving, non-myeloablative regimens, and HLA-typing , wider and more effective use of TSCS from compatible unrelated donors), the problems of TSCC-associated mortality in patients with chronic granulomatous disease, according to the latest they can be solved. In many cases, TSCC should be considered as a therapy for choosing patients with CGB, which allows to eliminate the very cause of its occurrence. The best results can be achieved in the case of TSCH from an HLA-compatible related donor, with the patient's early age associated with a better prognosis (less risk of infectious complications and GVHD).

[1], [2], [3], [4], [5], [6], [7]

Gene therapy

Currently, active research is underway, not only experimental, but also clinical, which showed the fundamental possibility of using gene therapy, both with X-linked and autosomal recessive forms of chronic granulomatous disease. There were first reports of successful cases of gene therapy in patients with chronic granulomatous disease.

Forecast

Over the past 20 years, the prognosis for patients with chronic granulomatous disease has improved significantly. The average life expectancy is 20-25 years with a mortality rate of 2-3% per year. The prognosis for patients whose first symptoms appeared after a year is significantly better than for those who had the disease started in the earliest childhood. The highest mortality is observed in early childhood. The most common cause of death are infectious complications. It should be noted that chronic granulomatous disease is a clinically heterogeneous disease, and its severity varies widely. In particular, it depends on the type of inheritance of the disease: it is generally accepted that patients with X-linked forms of chronic granulomatous disease a priori have the worst, in comparison with patients with autosomal recessive forms, but exceptions to this rule are described.

[8], [9]