IMMUNE CYTOPENIAS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (PECULIARITIES, PROGNOSTIC MARKERS)

Background: Immune cytopenia (IC) is one of the major complications in chronic lymphocytic leukemia (CLL). The paper describes the peculiarities of different immune cytopenia in CLL patients and the importance of individual prognostic markers in the course of the disease. Methods: We observed 62 patients with CLL complicated by immune cytopenia. Among these patients 30 had autoimmune hemolytic anemia (AIHA), 18 experienced immune thrombocytopenia (ITP), 10 had Fisher-Evans syndrome (FES), 3 were diagnosed with partial red cell aplasia (PRCA), and immune neutropenia (IN) was revealed in 1 patient. In addition to general examination and laboratory studies, the following examinations were performed: immunophenotyping of peripheral blood lymphocytes, flow cytometry (CD5; CD19; CD20; CD23; CD38; ZAP70), Coombs test, a molecular cytogenetic study of peripheral blood lymphocytes using the FISH method with TP53 and ATM probes, the level of ß2-microglobulin. Results: It was established that the overall survival of CLL patients with IC depends on the form of the latter. The median overall survival in patients with Fisher-Evans syndrome was the shortest (75 months), slightly better survival was observed in patients with AIHA (median 80 months), the best survival was found in patients with ITP (median not reached). Among unfavorable markers of CLL with IC, there is the presence of del 11q22.3. Unfavorable prognostic markers were also the following: a positive Coombs test, high levels of ZAP 70 expression, and high levels of ß2-microglobulin

Severe Hemolytic Disease of Newborn Due to Alloimmune Anti-E Antibodies: A Case Report

Hemolytic disease in the newborn (HDN) as a cause of early jaundice is mostly due to Rh (D), ABO incompatibility, and rarely due to other minor blood group incompatibility. We report case of Rh anti-E isoimmunization presenting as significant unconjugated jaundice within the 24 h of life. Baby presented with severe jaundice and anemia on day 1 of life. Baby was treated with intensive phototherapy, double volume exchange transfusion (DVET), and intravenous immunoglobulins. On evaluation, both mother and baby had O positive (Rh) blood group; however, the infant showed evidence of severe hemolysis. Positive direct Coombs test (DCT) and 11 cell antibody panel showed anti-E antibodies. This case highlights the importance of early identification and evaluation of HDN in the absence of Rh(D) and ABO incompatibility and possibility of severe hemolysis in Rh anti-E isoimmunization needing DVET.

MACROPHAGE ACTIVATION SYNDROME IN RHEUMATIC DISEASES IN CHILDREN: A RETROSPECTIVE STUDY

Macrophage activation syndrome (MAS) is a rare life-threatening complication of rheumatic diseases (RD) that requires early recognition and adequate immediate treatment. Objective of the study: to identify the features of onset of RD in patients who developed MAS, the clinical and laboratory characteristics of the MAS, possible trigger factors and the timing of development. Materials and methods of research: 57 patients (20 boys and 37 girls) with RD who developed MAS were included in a retrospective continuous non-randomized study: 36 (63%) with systemic juvenile idiopathic arthritis (sJIA), 19 (33%) with Systemic lupus erythematosus (SLE), 1 (2%) – with juvenile dermatomyositis (JDM), one (2%) – with overlapping syndrome. Results: in the structure of patients with sJIA, patients with a history of MAS accounted for 28%, among patients with SLE – 7,6%. The median age at the time of sJIA debut in the study group was 2,6 years [1,5; 5,75], patients with SLE – 11,8 years [8,6; 13,95]. The ratio of boys and girls in the study group was 1:1,85. 70 MAS episodes were recorded: 48 – with sJIA, 20 – with SLE, one episode each for JDM and crossover syndrome. A single episode of MAS at the onset had 22% of patients with sJIA, 47% – with SLE, MAS during the course of the disease – 55% and 47%, repeated episodes of MAS – 25% and 5% of patients, respectively. Clinical manifestations of MAS included fever in 91% of children, hepatomegaly in 54%, pericarditis in 51%, skin lesions in 68%, CNS damage in 44%, lung damage in 33%, hyperferritinemia in 96%, thrombocytopenia – in 79%, increased aminotransferases – in 89%, hypertriglyceridemia – in 53%. Patients with sJIA and MAS had statistically significantly earlier onset (p=0,047), a greater number of systemic manifestations (p=0,012), a typical exanthema (p<0,0001), and a smaller number of active joints (p=0,041). 83% of them had episodes of MAS before the initiation of therapy with biological disease-modifying antirheumatic drugs (bDMARDs). There was no statistically significant relationship between the development of MAS with the use of bDMARDs with a clear positive relationship with the violation of the therapy regimen. 19% of patients with sJIA and MAS had a history of infusion reaction to tocilizumab, 8% later had interstitial lung damage. Patients with SLE and MAS at the onset were statistically significantly more likely to have serositis (p=0,0028), ulcers of the oral mucosa (p<0,0001), neuropsychiatric disorders (p=0,0024), positive Coombs' test (p=0,026). All patients received glucocorticoid therapy; experience with the use of GIBP in the study group was limited. Conclusion: MAS in children develops more often with sJIA; the dominant provoking factor is the activity of the underlying disease. The overwhelming majority of patients developed MAS during the course of the disease, less often at the onset. Patients with a history of MAS with sJIA are characterized by an earlier age of onset, a predominance of systemic manifestations, the need for early administration of bDMARDs therapy, and a tendency to infusion reaction to tocilizumab. Against the background of bDMARDs, a subclinical course of MAS with the absence of fever is possible. The risk of developing MAS along with SLE is higher in patients with onset of serositis, ulcers of the oral mucosa, neuropsychiatric disorders, and a positive Coombs' test. MAS cases were detected with high SLE activity at the onset, violation of the treatment protocol.

Clinical and genetic characteristics of PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome

Objective To summarise the clinical and genetic characteristics of three children with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome. Methods This study retrospectively analysed the clinical and genetic data of three children with PAMI syndrome in our hospital between April 2018 and January 2020. Results One male and two female children were 6 years and 5 months, 8 years and 7 months, and 13 years and 3 months of age. All three patients had a recurrent blood trilineage hypoplasia and splenomegaly. Patient 1 had pyoderma gangrenosum, and Ludwig’s angina. Patient 2 had pyogenic arthritis, and pyoderma gangrenosum. Patient 3 had hepatomegaly, pyogenic arthritis, and pulmonary hypertension. Laboratory tests revealed that all three children had elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Patient 1: C-antineutrophilic cytoplasmic antibodies(c-ANCA), positive; antiglobulin test (Coombs), positive. Patient 2: blood zinc, 4.38 mg/L (elevated). Patient 3: Antinuclear antibodies (ANA), 1:100, β2 glycoprotein I, positive; Coombs test, positive; RF, 28.3 U/ml (elevated); C3, 0.77 g/L (decreased). Genetic testing showed that all 3 patients had PSTPIP1 c.748G > A (p.E250K) spontaneous heterozygous mutations, suggesting the diagnosis of PAMI syndrome. Patient 1 was treated with a combination of methylprednisolone and cyclosporine for 8 months. The patient did not develop new skin lesions. The blood count showed mild neutropenia. The spleen was considerably retracted and the CRP became normal. Patient 2 was treated with etanercept and methylprednisolone. The patient had no further arthralgias and pyoderma gangrenosum showed improvement. The spleen was smaller than before. White blood cells were shown to be approximately 2–3 × 109/L. The haematocrit, platelets, CRP, and AESR were normal. Patient 3 was treated with methylprednisolone, methotrexate, and infliximab 4 times. The patient’s joint symptoms disappeared gradually and the liver retracted markedly. The pulmonary artery pressure returned to normal. Moreover, Coombs test result was negative. CRP and AESR were lower than before. Conclusion PAMI syndrome can manifest as pyogenic arthritis, pyoderma gangrenosum, acne, and trilineage hypoplasia, as well as autoimmune diseases. Glucocorticoid and immunosuppressive therapy are partially effective and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing is helpful to confirm diagnosis.

MATERNAL AND FETAL OUTCOME IN RH NEGATIVE PREGNANCY

INTRODUCTION- When Rh negative maternal blood is exposed to Rh positive fetal blood (RBC) in maternal circulation, antibodies against Rh (D) may develop in the mother. These Rh (D) antibody, once produced, remains in the woman's circulation and poses the threat of hemolytic disease (due to destruction of fetal RBCs ) for subsequent Rh-positive fetuses and this event leads to alloimmunization. Coombs test is the most common method to detect alloimmunization done during pregnancy (ICT) and in postnatal period (DCT). Rhesus (Rh) isoimmunization is an important clinical entity in India and other developing countries, which is responsible for fetal anemia and hydrops fetalis, and if not treated, it can result in intrauterine fetal demise, thus timely diagnosis follow-up and management of Rh –ve pregnancy is must. MATERIAL AND METHODS- st th This is a retrospective observational study, done in a private hospital, Gwalior (M.P.), form 1 Jan. 2018 to 30 June 2020. 88 women with Rh-ve pregnancy were studied during this period, Data was recovered from labor room record, OT, PNC, post operative wards for maternal outcome a SNCU for neonatal outcome. RESULTS- In our study the most common age group was 21-25 years (62.5%), most of the patient were Primigravida(42.4%), most of them were unbooked (65.90%) and from Rural area (72.72%). The most common blood group Rh- was o-ve (53.40%). Only 2 patients had positive indirect coombs test. Most of the patients delivered normally, only (28.40%)Patients delivered by LSCS. Preeclampsia was the most common maternal complication found in Rh- Patient (12.5%). 96.59% of Neonates were live born. 2.27% were fresh still born and 1.13% were macerated still born. 24 babies were admitted in SNCU. The most common cause of admission was neonatal jaundice (66.66%). The most (76.13%) of the babies had serum bilirubin level between 10-15 mg/dl. CONCLUSION- We concluded that Rh isoimmunization leads to increased perinatal morbidity for perinatal morbidity. The obstetrician and maternity staff should be familiar to diagnosis and management of with Rhesus incompatibility and they should counsel the Rh negative patient about Importance of checking blood group and Rh type in pregnancy and should educated them about importance of Rh prophylaxis and Hemolytic diseases of fetus and newborn risks of present and future pregnancy. During past few decades there had been major advances in the medical treatment for Rh negative pregnancy.

Autoimmune myelofibrosis associated with autoimmune hemolytic anemia successfully treated with ruxolitinib

A 55-year-old man suffered from dyspnea, general malaise, and jaundice. His laboratory date showed pancytopenia and hemolytic anemia, and computed tomography showed splenomegaly. Bone marrow examination revealed myelofibrosis (MF)-1. The hemolytic anemia was diagnosed as IgM autoimmune hemolytic anemia (AIHA) with negative direct and indirect Coombs test but positive IgM-direct antiglobulin test. We started ruxolitinib 20 mg, which improved not only bone marrow fibrosis, symptoms related to myeloproliferative neoplasms and splenomegaly, but also AIHA. AIHA may be associated with Autoimmune MF (AIMF), and cytokines such as transforming growth factor (TGF)-β are thought to be involved in such cases. This case suggests that ruxolitinib may improve the cytokine levels and may lead to the treatment of AIHA as well as AIMF.

Childhood Onset Systemic Lupus Erythematosus with Direct Coombs Test Positive in the Absence of Hemolytic Anemia – A Rare Case Report

Systemic Lupus Erythematosus being a chronic autoimmune multisystem inflammatory disease, affects predominantly women of reproductive age group. Childhood – Onset Systemic Lupus Erythematosus is a rare disease with an incidence of 10% - 20%. Positive direct Coombs test in the absence of hemolytic anemia indicates high disease activity and severe renal damage. Herein we report a case of 11-year-old female child diagnosed as Systemic Lupus Erythematosus with positive direct Coombs test in absence of hemolytic anemia which is very rare.

Clinical characteristics and genetic analysis of A20 haploinsufficiency

Purpose To evaluate the clinical and genetic characteristics of 3 children with Haploinsufficiency of A20 (HA20). Methods:The clinical and genetic testing data of 3 children with HA20 treated at Capital Institute of Pediatrics (CIP) between August 2016 and October 2019 were retrospectively analysed. Result Patient 1 presented with arthritis and inflammatory bowel disease, patient 2 presented with axial spinal arthritis and lupus-like syndrome, and patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses. Regarding laboratory tests, patients were found to have elevated white blood cell (WBC) count, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The CRP and ESR was reported to be high in all the patients. The WBC was reported to be high in patient 1 and 3. Patient 2 was positive for antinuclear antibodies, anti-Sjögren’s syndrome antigen A, dsDNA, rheumatoid factor and Coombs test. Genetic testing showed that all three patients had heterozygous mutation in TNFAIP3 gene. As for the treatment, patient 1 was treated with TNFα antagonist, patient 2 was treated with TNF α antagonist and sulfasalazine, and patient 3 was treated with corticosteroids and thalidomide. Patients 1 and 2 were followed for four and 3 months, respectively. There was an improvement in joint and gastrointestinal symptoms; inflammatory indices and rheumatoid factor (RF) were normal, and dsDNA and Coombs test became negative. Patient 3 was treated at another hospital and showed gradual improvement in oral ulcers and perianal abscesses. Conclusion HA20 is a single-gene auto-inflammatory disease caused by mutation in tumour necrosis factor (TNF)-α-induced protein 3 (TNFAIP3) gene. It may present as Behçet-like syndrome and resemble various other autoimmune diseases as well. Corticosteroids and immunosuppressive agents are effective treatments, and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing should be proactively performed for children with early-age onset or Behçet-like syndrome to achieve early diagnosis and accurate treatment.

EPIDEMIOLOGY AND RISK FACTORS OF WARM AND COLD AUTOIMMUNE HEMOLYTIC ANEMIA

Even though clinical features in autoimmune haemolytic anaemia vary according to the type of AIHA, anaemic syndrome stays common for most of the cases. A positive Coombs test or direct anti-globulin test developed in 1945 by Coombs, Mourant and Race, is the most deciding factor in AIHA diagnosis. Since the immunologic mechanisms causing erythrocyte destruction vary between AIHAs, treatment is also different. Empirical approach with glucocorticoids is the main treatment of AIHA overall, but less effective in CAD. However, the current medical literature is still with gaps concerning the management, presentation and diagnosis of the different types of AIHA altogether.