Treatment of chronic granulomatous disease

Treatment for patients with chronic granulomatous disease includes:

• Prevention of infections through immunization and avoidance of contact with possible sources of infection.
• Preventive continuous use of trimethoprim-sulfamethoxazole at a dose of 5 mg/kg per day of trimethoprim and antifungal drugs (itraconazole 200 mg/day per os, but not more than 400 mg/day).
• As early as possible, antibacterial and antifungal therapy should be initiated parenterally in high doses when infectious complications occur. The duration of therapy depends on the severity of the disease and can range from several weeks (for purulent lymphadenitis) to several months (for liver abscesses).

In case of aspergillosis, long-term therapy with amphotericin (preferably liposomal) at a dose of 1-1.5 mg/kg per day was previously used. However, the frequency of aspergillosis resistance to amphotericin remains high, in addition, the drug's safety profile is a limiting factor for its use. Therefore, in recent years, new antifungal drugs have become increasingly widespread, which have demonstrated their activity in numerous clinical studies on 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, combination therapy with both drugs is recommended (for example, in the case of manifestation of a fungal infection after HSCT).

For nocardiosis ( Nocardia asteroides ) - high doses of TMP/SMK, if ineffective - minocycline or amikacin+IMP. Nocardia brasiliensis - AMK/CL or amikacin+ceftriaxone.

4. Surgical treatment in the case of superficial abscesses (purulent lymphadenitis) - the use of this method is significantly limited. In case of liver and lung abscesses, conservative treatment with high doses of antibiotics and antifungal drugs is effective in most cases, and surgical opening 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. Use of granulocyte mass obtained from donors stimulated with G-CSF.
6. The use of high doses of g-interferon (adult dose 50 mcg/m2 ^{subcutaneously} 3 times a week, for children: with a body surface area of <0.5 m2 ^- 1.5 mcg/kg subcutaneously 3 times a week, with a body surface area of >0.5 m2 ^- 50 mcg/m2 ^{subcutaneously} 3 times a week) in some patients reduces the frequency and severity of infectious manifestations.
7. In the formation of obstructing granulomas - glucocorticoids together with antibacterial therapy.

Bone marrow transplant/hematopoietic stem cell transplant

Previously, bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HSCT) in patients with chronic granulomatous disease was accompanied by a fairly high failure rate. Moreover, this was often associated with an unsatisfactory pretransplant status of patients, in particular, with a fungal infection, which, as is known, along with GVHD, occupies one of the leading places in the structure of post-transplant mortality. However, recently, due to the expansion of the arsenal of effective antifungal drugs and a decrease in the frequency of fatal mycoses, as well as due to the development of the HSCT technology itself (this concerns, for example, new organ-preserving, non-myeloablative conditioning regimens, as well as the improvement of HLA typing and, in this regard, a wider and more effective use of HSCT from compatible unrelated donors), the problems of HSCT-associated mortality in patients with chronic granulomatous disease, according to recent publications, can be solved. In many cases, HSCT should be considered as the therapy of choice for patients with CGD, which allows eliminating the very cause of its occurrence. The best results are achieved in the case of HSCT from an HLA-compatible related donor, while early patient age is associated with a better prognosis (lower risk of infectious complications and GVHD).

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Gene therapy

Currently, active research is being conducted, not only experimental but also clinical, which has shown the fundamental possibility of using gene therapy, both in X-linked and autosomal recessive forms of chronic granulomatous disease. The first reports of successful cases of gene therapy of patients with chronic granulomatous disease have appeared.

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 one year is significantly better than for those whose disease started in early childhood. The highest mortality is observed in early childhood. Infectious complications are the most common cause of death. 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 a worse prognosis compared to patients with autosomal recessive forms, but exceptions to this rule have also been described.

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