Girl R., 8 years old (date of birth – November 24, 2013), born from the 4th pregnancy against the background of a burdened obstetric history (her mother had 2 miscarriages at an early stage), 2 urgent deliveries. Birth weight — 3660 g, Apgar score — 8/9 points. Preventive vaccinations according to an individual calendar (BCG, V1 against polio, V1–V2 against viral hepatitis B). The child suffered from the following diseases — chickenpox in 1 year 10 months, acute respiratory viral infections, follicular sore throat, acute bronchitis, acute tonsillitis, infectious mononucleosis. The heredity for hematological, immunological, and oncological diseases was not burdened.
The patient has been ill since the age of two, when, after chickenpox, a fever attack of up to 40 degrees first appeared, accompanied by an increase in the palatine tonsils, the appearance of purulent plaque on them, and an increase in cervical lymph nodes (Figure 1). This attack was regarded as an infectious process, stopped by antibacterial therapy and the use of nonsteroidal anti-inflammatory medicines (NSAIDs).
Рисунок 1. Налеты на небных миндалинах в приступный период (собственное наблюдение)
Figure 1. Raids on the palatine tonsils during the onset period (own observation)
However, then such episodes began to recur every 20–30 days with the duration of the attack 5–7 days. There was an intestinal syndrome in the form of abdominal pain, nausea, vomiting, loose stools, arthralgia, and an increase in inflammatory activity of the blood (ESR up to 28 mm/hour) began to join the temperature and increase in the tonsils.
Outside of the attack, the patient showed a satisfactory condition. Her physical development was harmonious according to the mesosomatic type. All the internal organs were without features. Physiological recovery was normal.
During the year, there was a positive effect during attacks in the form of fever relief after taking NSAIDs.
From the age of three, the patient has been observed by an immunologist with a diagnosis of Marshall syndrome; dysgammaglobulinemia was detected as well. During the attacks, she took glucocorticosteroids (GCS) (Prednisone orally 1 mg/kg with a positive effect). At the age of 6, she was consulted by a rheumatologist, therefore, immunological studies were carried out (extractable nuclear antibodies, antibodies to cardiolipin (total), antibodies to single-, double-stranded DNA, antibodies to cyclic citrullinated peptides, antibodies to phospholipids); all the indicators were within normal limits. There was not any data on autoimmune pathology. During the attacks, it was recommended to take GCS (metipred) (1.5 mg/kg). Further, due to a decrease in the response to GCS, the dose of Prednisone was gradually escalated to 2 mg/kg during attacks.
Taking into account the long course of the disease and the short intervals between attacks and the response only to an increase in the dose of GCS to 2 mg/kg at 7.5 years of age, a molecular genetic study was conducted, as a result of which a mutation in the MVK gene was detected in the 11th exon (V377I) and the 9th exon (I268T) in a heterozygous state. This confirms the diagnosis of mevalonate kinase deficiency syndrome.
In order to determine further management tactics, the patient was sent to the Department of Immunology of the Federal State Budgetary Institution “National Medical Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev” of the Ministry of Health of Russia, where she was hospitalized in July 2021.
Upon admission, the somatic status was stable, there was moderate hypertrophy of the tonsils (1–2 degrees) with a single plaque.
Laboratory test results:
Results of instrumental research methods:
Medical conclusion: the examined biopsy material showed signs of active erosive ileitis, inactive reactive colitis. There were no signs of amyloidosis.
Consultation by an ophthalmologist — OU without pathological changes.
The diagnosis was “Primary immunodeficiency condition: autoinflammatory syndrome — mevalonate kinase deficiency syndrome (mutation in the MVK gene in exon 11 (V377I) and exon 9 (I268T) in a heterozygous state)”.
This disease is chronic in its nature; in the absence of control of inflammatory attacks, the risk of developing kidney amyloidosis and multiple organ failure and other life-incompatible complications is high.
Taking into account the severity of the disease course, as well as the presence of recurrent episodes of high fever in the patient, accompanied by an increase in the palatine tonsils, intestinal syndrome, nausea and arthralgia, as part of achieving and maintaining remission, the girl was prescribed a monoclonal inhibitor IL-1b Kanakinumab (Ilaris) at a dose of 75 mg once every 8 weeks, subcutaneously, according to vital indications.
Already after the first administration of the medicine, the attack-free interval increased to 50 days.