FSI FSCC PHOI n.a. D.Rogachev

FSI "FSCC PHOI n.a. D.Rogachev"

Ministry of Health

Address and postal address:
117198, Moscow, 1 Samory Mashela Street
Phone number: [phone]

Ministry of Health of Russian Federation
Federal State Budget Institution "Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev"
(FSI "FSCC PHOI n.a. D.Rogachev" Ministry of Health)

17 March 2014

№758

Moscow

Discharge summary №2014/832

Britzov Gleb Dmitryevich, (1 year and 10 months of age) born on 28.03.2012, residing at Moscow, 8 Cshorsa Str., apt. 4, receives medical treatment in the pediatric hematology/oncology department from
13.02.14 till now with the diagnosis of Primary immunodeficiency (chronic granulomatous disease).
Complications - invasive fungal infection of the lungs (aspergillosis?), inflammation after BCG vaccination.
Complaints on admission: mother has none.
Medical history: mother began to notice bloodstreaks periodically since the child was 2 months of age. FBC showed leukocytosis 24*10⁹/ L, in connection with which the child was hospitalized in Clinical hospital for the infectious diseases of children №4, where the child received treatment for anemia and rotaviral infection (antibiotic treatment - ceftriaxone).
The child's condition is without changes. FBC showed marked leukocytosis with left deviation (myelocytes, metamyelocytes, the appearance of normoblasts in the peripheral blood 2:100). The child
was transferred to the City clinical hospital № 9. The condition at the admission was severe due to anemia, intoxication.
The examination revealed anemia up to 60 g/l, leukocytosis max up to 42*10⁹/L, with deviation to metamyelocytes, eosinophilia, increased ESR. The myelogram showed hypereosinophilia, no atypical cells. According to ultrasound investigation report - splenomegaly. PCR of CMV in urine was positive, therre revealed high numbers of IgM to CMV, the child received medical maintenance with ganciclovir.
The medical maintenance also included antibacterial therapy (Maxipime, Meronem, Edizin, Zimiven).
During therapy the child developed purulent periproctitis, surgery was carried out on the occasion of that.
For further examination and treatment, the child was hospitalized in FSCC PHOI n.a. D.Rogachev (first hospitalization on 22.06.12 at the age of 2 months and 3 weeks), a differential diagnosis was provided between Chronic myeloid leukemia and Juvenile myelomonocytic leukemia, hypereosinophilic syndrome, but these disease were excluded based on the survey data, the child was managed for a long time with the diagnosis of chronic myeloproliferative unspecified disease, taking into account leukocytosis, hepatosplenomegaly. The child developed iron deficiency anemia, in connection with which he received therapy with iron preparation per os without effect (Hb 70 g/L, serum iron 2.5 - 4.5 µmol/L).
During observation in FSCC received 3 transfusion of red cells 10 mg/kg on 22.06.12, 29.06.12, 05.07.12.
In March 2013, during a routine abdominal cavity organs ultrasound the mass was found, the child
was also examined by gastroenterologist with suspected Crohn's disease, nonspecific ulcerative colitis?
In October 2013 the child was hospitalized in the Surgery Department of FSCC, according to the
instrumental examination including abdominal cavity organs ultrasound, abdominal cavity organs CT, esophagogastroduodenoscopy, colonoscopy with floor-by-floor biopsy no data confirming Crohn's disease/nonspecific ulcerative colitis were received; the marked lymphoid hyperplasia all throughout colon was observed. Histopathology Report: within the investigated material revealed presentation of the mild inactive colitis, no data confirming Crohn's disease were revealed. Just according to the examination enterokistoma was suspected, there identified a large number of enlarged lymph nodes in the abdominal cavity. Duplication gastrointestinal cyst was suspected, the child was discharged under the observation, it was decided to abandon more invasive methods of investigation (laparoscopy?) at that time.
From 31.10.13 to 02.11.13 considering the heavy IDA (Hb 70 g/L, MCV 69 fL, erythropoietin 129 mIU/mL, serum iron 4.4 mmol/L), was conducted such therapy as Venofer I.V. (260 mg/course), with the positive response, the hemoglobin level rose to 94 g/L.
The child continued to be watched in the FSCC clinic; during the observation reducing the liver size, spleen size normalization, decreasing the leukocyte count to 24*10⁹/L were noted.
Over time according to the ultrasound report from December 2013 negative trend was observed in the form of increasing of the mass size, it also acquired polycystic form.
From 20.01 to 28.01.14 was admitted to the Gastroenterology Department of Russian children's clinical hospital, Moscow with a diagnosis of chronic colitis of unspecified etiology, enterokistoma? From 28.01 to 12.02 was admitted to the Abdominal surgery department of Russian children's clinical hospital with a diagnosis of enterokistoma, lymphadenopathy of the abdominal lymph nodes, the biopsy of the abdominal cavity lymph nodes in conditions of Oncologic Department was recommended.

To conduct further examination, verification of diagnosis and exclusion of solid neoplasms the patient was hospitalized in Pediatric hematology/oncology Department.

Life history: child of the first pregnancy, physiologically proceeded. In the early second trimester of the pregnancy IgG to CMV were revealed, therefore mother of the patient received a course of treatment with Viferon 1 million. Spontaneous vaginal delivery, birth in time at 38 weeks. Birthweight - 2960g, length 50 cm. BCG vaccination was provided in maternity hospital. The patient has no siblings.

Condition on admittance - 13.02.14.
Height - 83 cm, weight 11 kg.
Condition – severe due to prior disease.
T-36.0 C
HR 100 per min, systolic blood pressure - 90.0 mm Hg, diastolic blood pressure - 60.0 mm Hg.
General well-being - is not impaired. Child is active, walking, playing in a good mood. Consciousness is clear. Skin integuments – pale with no rash. The visible mucous membranes of the oral cavity covered with white fur (fungal infection?), aphtha on the upper lip. Inflammation after BCG vaccination was identified, as well as regional lymphadenitis. Lymphatic system examination showed following - submandibular lymph nodes up to 2 cm, axillary lymph nodes to the left up to 1.5 cm. Respiratory tract examination showed following – no nasal respiratory stress, puerile breath in the lungs can be heard, auscultated over all regions, no rales. Circulatory system examination showed following - clear rhythmical heart tones. Digestive system - moist tongue, the edges covered with white fur (fungal infection?). Liver + 2 cm, spleen is not palpable.
Urinary system - natural painless urination.
Clinical diagnosis: Iron deficiency anemia? Abdominal mass?

Survey report:
1. Blood group B (III), Rh positive. Coomb's test negative.
2. Haemogram - WBC 14.2*10⁹/L (PMN 56.2%, LYM 29.6%, MON 11%), Hb 94 g/L, PLT - /? неразборчиво/*10⁹/L.
3. Biochemistry of blood from 14.02 - Slight increase of ALT 51 U/L (0-31), other indicators are within normal limits: ferritin 258 µg/L (6-60), serum iron - 2.8 µmol/L (9-21), TIBC 39.8 µmol/L (27.8–63.0), transferrin 2.18 g/L (2-3.6), soluble transferrin receptor 1.45 mg/L (0.76-1.7), erythropoietin 50.85 mIU/mL (3.22-31.9). Over time - from 27.02 - ferritin 105 µg/L, serum iron 5.1 mol/L, traisferrin 1.53 g/L.
CRP from 14.02 - 59 mg/L (0-5).
Immunoglobulin A 1.66 g/L (0.1-1), IgG 17.3 g/L (4.6-14.6), IgM 1.56 g/L (0.6-1.8).
4. Coagulation - within normal limits.
5. OncoMarkers- intact HCG, alpha-fetoprotein, cancer Ag antigen 19-9, carcinoembryonic Ag antigen - within normal limits, neuron - specific enolase 15 µg/L (0-13), CA 242 - 7.9 U/ml.
6. Myelogram - punctate from 4 points - rich, polymorphic composition. Megakaryocytic germ is arratated, megakaryocytes "lace" platelets. Neutrophil germ is narrowed. Erythroid germ is expanded. Lymphoid and monocyte germ expanded.
7. Peripheral blood immunophenotyping from 14.02.14. (WBC 14* 10⁹/L) - a slight decrease in T-lymphocytes (CD3) 1.379 % (1.46-5.44), B-lymphocytes (CD19) 15.9% (19-31), increased NK-cells, 26.2% (7.5-18.7), double negative T-cells within normal limits.
8. Cytogenetic study of the bone marrow - from 14.02.14 - 46 XY.
9. CT of the lungs from 20.02.14. In S4 of the middle lobe of the right lung a seal portion of the lung tissue of irregular shape is noted, with indistinct and irregular contours, located in the basal and subpleural regions. Its structure is heterogeneous with the presence of irregularly extended bronchi; in contrasting uneven accumulation of the contrast agent is registered with the presence of hypodensive and actively contrast-enhancing regions. No signs of trachea and major bronchi obstruction. Mediastinum is not biased and expanded. The structures of the mediastinum are clearly differentiated. No enlarged lymph nodes of the mediastinum, free fluid in the pleural cavity and bone destructive changes were found. In axillary regions on both sides increased to 10 mm lymph nodes are revealed; single lymph node in the left axilla was found, partially calcined with the size of 10*7*16 mm.
Conclusion: circumscribed focus of inflammatory infiltration in the middle lobe (S4) of the right lung, the destructive nature can not be excluded (invasive mycosis?).
10. CT of the abdominal cavity from 20.02.14. In comparison with the previous study (from 21.10.2013 and 29.10.2013) negative dynamics is registered. The detected earlier cystic
mass persists, whose dimensions in the dynamics increased to 27*23*26 ​​mm (in the previous
study they were 22*18*22 mm). However, in the present study the revealed formation shifted closer to the gate of the liver and is located above the body of the pancreas - probably due to overstretched bowel loops. The structure of the mass in the present study is multicystic, with active contrast-enhancing over the capsule.
The walls of the small intestine are unevenly thickened, sealed, preferably in the duodenum. The mesenterial subcutaneous tissue is nonhomogenous and unevenly sealed. We are getting the impression that similar cysts exist in the mesentery of the small intestine - lymph nodes with the necrosis? The colon loops are overstretched, with significant amount of contrast agents and gases. Plenty of small hypodensive foci appeared in the liver parenchyma with the size of 5 mm, contrast-enhancing at the periphery. The liver did not change in size (vertical dimension - 100 mm). Intra-and extrahepatic bile ducts are not dilated. Portal system is not dilated. Gallbladder is typically located, former size, with a flexure in the neck, its walls are not thickened, no radiopaque stones in its lumen were observed. Spleen is still increased (vertical size - 98 mm), has smooth contours and homogeneous structure. The pancreas is typically located, its dimensions are: the head - 22mm, body - 11mm, caudal dimension - 14mm, the contours are smooth, clear, homogeneous in structure. Pancreatic duct is not expanded. Epinephros are of normal shape and position with homogeneous structure. Kidneys are not increased, the contours are smooth and precise. Cortico-medullary differentiation is preserved. Pyelocaliceal systems are not dilated on both sides. No radiopaque concretions in the kidneys' cavity systems and ureters are registered. Timely contrast evacuation.
Significant amount of the lymph nodes of the previous form, size and structure present in the abdominal cavity and retroperitoneal space. Adequate filling of the bladder, its walls are of uniform thickness. No intraluminal additional entities are defined. Free fluid in the abdomen and pelvic cavity is not defined. No bone destructive changes.
Conclusion: The negative dynamics from 29.10.2013 in the form of increased number of cystic formations in the abdomen on the right and the appearence of multiple small foci in the liver parenchyma - revealed changes are likely of infectious nature. Similar cystic formation in the mesentery of the small intestine (lymph nodes with destruction?).
Splenomegaly. Multiple enlarged lymph nodes in peritoneal cavity and retroperitoneal space.
In comparison with the investigation performed on 06/02/2014, provided in another medical preventive institution, without visible dynamic changes.
The investigation was provided with the consult of the head of Department of CT and MRI, MD Tereshchenko GV.

11. Ultrasound of the abdominal cavity from 17.02. LIVER: Dimensions: not enlarged, the right lobe vertical size is 96 mm, the vertical size of the left lobe is 71 mm. Contours: smooth, crisp, corners are not increased. Structure: homogeneous. Average echogenicity. Vessels: gate vienna and its branches are not changed, VCI and hepatic veins with no abnormalities. Intra- and extrahepatic bile ducts are not dilated. Multiple hypoechoic heterogeneous rounded, avascular, with indistinct contours, maximum size of 5*6 mm masses are revealed in both lobes of the liver parenchyma. GALLBLADDER: S-shaped in structure. The walls are not thickened. The fel in the lumen of the bile is homogeneous. PANCREAS: dimensions: head - shielded by gases, body-7 mm, caudal dimension - 11 mm (not increased). Contours: smooth and sharp. Structure: homogeneous. Echogenicity: average. Spleen: typically located. Dimensions: 105*32 mm, increased in size. Contours: smooth, clear. Structure: homogeneous. Echogenicity: average. Right kidney dimensions: 70*32 mm. Contours are smooth and sharp. Parenchyma: 9 mm, differentiation is saved. Calices-pelvis system is not dilated. Blood flow during CDI up to the capsule. Left kidney. Dimensions: 73*35 mm. Contours are smooth and sharp. Parenchyma: 12 mm, differentiation is saved. Calices-pelvis system is not dilated. Blood flow during CDI up to the capsule. Urinary bladder with no abnormalities.
Notes: multiple lymph nodes of medium echogenicity with maximum size of 19*12 mm are observed at the gate of the liver. Multiple mesenteric rounded in shape lymph nodes with maximum size of 12*5 mm with low echogenicity and aortocaval lymph nodes with size of 15*7 mm of average echogenicity are observed.
In the right segment of the abdomen a hypoechoic mass is visualized, with inhomogeneous structure, irregularly shaped with irregular un sharp contours and multiple cystic cavities (located most likely in the mesentery of the small intestine), wit the size of 34*23*40 mm. The mass is well vascularized at the periphery, the central part is practically avascular.
Conclusion: US-signs of the mass in abdominal cavity, focal lesions of the liver, splenomegaly, intra-abdominal and retroperitoneal lymphadenopathy.
12. Bronchoscopy - no signs of trachea obstruction, mucosa is edematous, vascular pattern is strengthened. The bifurcation region of normal form, Karina is acute and labile. Mouthes of 1-4 orders bronchi are free, their spurs are sharp and labile. Visible bronchial mucosa is edematous, diffusely hyperemic with contact bleeding. The cartilaginous rings relief is saved. Bronchial secretion of mucous viscous structure, of moderate amount.
Performing washings (cytology) yes - conclusion - there are a small number of coccal bacterial population. Against the background of mucus and cellular debris epithelial cells lying separately and accumulated are abserved (villous and flat), as well as macrophages.
Biopsy was not performed.
The bronchoalveolar lavage was is performed.
Conclusion: endobronhitis.
13. UA with no abnormalities.
14. Chest x-ray examination from 28.02.14 in direct projection in a standing position.
Condition after catheterization of the right subclavian vein. The distal end of CVC is
determined in the projection of the right atrium. In the projection of the middle lobe of the right lung
locus of the seal lung pattern with indistinct and irregular contours is observed.
Throughout the rest of the lung the lung pattern is enriched with interstitial component. Lung hilum are not visualized due to the mediastinum shadow. The shadow occupies a middle mediastinum position, with no abnormalities. Cupula of the diaphragm is typically located, clear and smooth. Pleural sinuses are free.
Conclusion. This changes in the right lung should be differentiated between circumscribed focal inflammatory infiltration or changes of fungal etiology.
15. Chemiluminescence of neutrophils from 18.02.14.
- spontaneous chemiluminescence in the presence of luminol, mV/min - 1.8 (N 10-30)
- in the presence of luminol chemiluminescence induced by zymosan, mV/min - 12 (N 100-300)
- spontaneous chemiluminescence in the presence of lucigenin, mV/min – 0.6 (N 1.3-5.8)
- in the presence of lucigenin chemiluminescence induced by zymosan mV/min - 2.7 (N 17-38)
The test was repeated on 28.02.14, all the indicators were also descreased.
16. Blood genetic study from 21.02.14. In the 10th exon of the gene CYBB revealed replacement of
GGG→CGG c. 1165, leading to a substitution of glycine by arginine at codon 389 (Gly389Arg, G389R), in the hemizygous state (X - chromosome). This substitution is described in a CYBBdatabase in one patient with a chronic granulomatous disease.
During the analysis of (1/9, 11/13) exons of the CYBB gene and adjacent intron areas were found no mutations resulting in a change of amino acid sequence.
16. Infectious Diseases Diagnosis
1. Bronchoalveolar lavage bacterial inoculation for flora - Pseudomonas aeruginosa (responsive to piperatsilin/tazobactam), Streptococcus pneumonia. Positive galactomannan 1.33. CMV positive.
2. Blood – CVM, EBV - neg. Bone marrow - CMV, parvo B19 – neg.
3. Feces (bacterial inoculation for flora) – Enterococcus faecium VRE, Escherichia coli ESBL (resistant to levofloxacin, piperatsilin/tazobactam, ceftazidime/sulbactam, ciprofloksan, ertapenen), Pseumodas aeruginosa (interjacent sensitivity to meropenem).

17. Specialty consultations:
1. Neurologist from 06.03.14 - the main clinical diagnosis: D50.8 Psycho-motor development according to age.

2. Ophthalmologist from 06.03.14 - in transmitted light no fundus pathology is revealed.

3. Otorhynolaryngologist from 11.03.14 - at the time of inspection no data for acute ENT pathology revealed.

Thus on the basis of the survey the child was diagnosed the primary immunodeficiency (chronic granulomatous disease), history of paraproctitis, granulomatous? colitis, inflammation after BCG vaccination, pulmonary aspergillosis?, chemiluminescence data. Diagnosis was genetically confirmed.

On 24.02 CVC (Certofix) was replaced, antibacterial therepy was provided (tazocin 300 mg/kg/s), antifungal therapy was given (vifend 18 mg/kg/s) taking into account pulmonary involvement. On 04.03 CVC was removed by the patient for future treatment 05.03.2014 CVC Port-A-Cath was installed.
Taking into account ineffective erythrogenesis, mixed genesis of anemia (Anemia of chronic disease+ iron-deficient anemia) 12.03.14 /неясно из контекста/ 25 mcg (2.25 mg/kg) is given 1 time per week.

At the moment the child's condition is severe due to main disease, well-being is not bad, afebrile. Twenty-four-hour infusion therapy is performed, intravenous antibiotics and antifungal therapy. It is planned to conduct a follow-up examination (lung CT, abdomen cavity CT, ultrasound investigation) to assess the effectiveness of therapy and the patient's transfer to a specialist unit (Immunology Department of FSCC) for specific therapy and a decision on the transplantation of hematopoietic stem cells. The child currently can not be discharged from the hospital, and therefore we request the social security authorities to consider absentee disability extension of residence under the current legislation.

Deputy Chief Doctor Lytvinov DV

Deputy Head of Dep. Baidyldyna DD

Consulting physician Kalynina II

Stamp

/неразборчиво/


17.03.2014

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