Successful Use of Anifrolumab and Baricitinib Combination Therapy in an Infant with Spondyloenchondrodysplasia with Immune Dysregulation (SPENCD-I)

Remembering Other Causes of Alveolar Siderophages: Macrophage Activation Syndrome

Severe neonatal thrombocytopenia due to fetomaternal anti-A alloimmunization: A case report

Neonatal thrombocytopenia is a common hematological problem but refractory thrombocytopenia is very rare in neonates. A systematic and diligent workup will result in arriving at the proper diagnosis and providing accurate management in rare causes of neonatal thrombocytopenia. We report a case of severe refractory thrombocytopenia in an extremely low birth weight (ELBW)/extreme preterm baby who presented with early onset severe thrombocytopenia associated with anemia and required multiple platelet transfusions. After ruling out COVID-19 infection, sepsis and neonatal alloimmune thrombocytopenia (NAIT), the cause for severe refractory thrombocytopenia was diagnosed as Type II congenital amegakaryocytic thrombocytopenia (CAMT) by bone marrow examination and MPL gene mutation studies.

Hemophagocytic Lymphohistiocytosis.

The concentrations of uranium, nickel, cobalt, copper, vanadium, calcium, sodium, and potassium in the natural waters were determined and their distribution patterns interpreted in the light of the geology of the area. The climatic and hydrological conditions prevalent there and the geochemical behavior of the elements were also considered. (TCO)

A RARE CASE OF ACUTE LIVER FAILURE, HEPATITIS ASSOCIATED APLASTIC ANEMIA, AND HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

Idiopathic Thrombocytopenic Purpura

Between a rock and a hard place.

HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS DISGUISED AS A PULMONARY EMBOLISM IN A YOUNG MALE

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by uncontrolled macrophage activation in the setting of dysregulated natural killer cells and cytotoxic lymphocytes, leading to hypercytokinemia and severe inflammation. HLH can be primary, from genetic mutations, or secondary, triggered by infections, malignancy or autoimmune diseases. The estimated incidence of HLH in 2019 was 13 per 100,000 admissions. In recent years, several case reports have also documented HLH following coronavirus disease 2019 (COVID-19) infection, where the suspected pathogenesis is immune dysregulation and macrophage activation triggered by lingering inflammation. Here, we present a case of HLH following a recent COVID-19 infection. A 61-year-old female with rheumatoid arthritis presented with worsening diarrhea following a COVID-19 infection 2 weeks prior. Home medications included hydroxychloroquine and methotrexate. During the hospitalization, she developed a diffuse maculopapular rash, fevers up to 103.6°F, and dyspnea, despite empiric antibiotics and oral prednisone. Labs showed elevated ANA, CRP, ferritin (>33,500 ng/mL), aldolase and triglycerides (193 mg/dL), transaminitis, anemia, thrombocytopenia, and normal fibrinogen (340 mg/dL). Infectious work-up including blood cultures, repeat COVID PCR, respiratory viral panel, sputum cultures, beta-D-glucan, and endemic fungal work-up, were negative. A repeat CT chest revealed new bilateral ground-glass opacities (GGOs) and bilateral perihilar, mediastinal, and axillary lymphadenopathy. A bronchoscopy with bronchoalveolar lavage revealed neutrophilic bloody return with negative cultures, prompting a course of pulse-dose steroids for the concern of diffuse alveolar hemorrhage. Skin rash biopsy revealed sparse perivascular and interstitial lymphohistiocytic infiltrate within the dermis, consistent with cutaneous HLH. Albeit a bone marrow biopsy showed hypercellularity without hemophagocytosis. Follow-up labs confirmed HLH with elevated CXCL9 (16,092 pg/mL) and soluble IL-2R (2614 U/mL). An 8-week dexamethasone taper was initiated for HLH treatment with subsequent clinical improvement. Diagnosing HLH is challenging due to its nonspecific clinical manifestation. In cases like this, of multi-organ disease or fever of unknown origin, HLH and other hyperinflammatory syndromes should be considered. HScore is a useful tool for assessing the likelihood of HLH. In this case, further tests and biopsies proceeded given an HScore predicting 88-93% probability of HLH. Skin biopsy rarely reveals hemophagocytosis, but as demonstrated in our case and three other reported cases, skin biopsy findings are suggested to have a crucial role in prompt diagnosis when bone marrow biopsy is inconclusive or unavailable.

Hemophagocytic Lymphohistiocytosis in B-Cell Lymphoproliferative Disorder: Report of a Rare Association

Hemophagocytic Lymphohistiocytosis in a Extremely Low Birth Weight Infant Presenting with a Neonatal Thrombocytopenia.

<p>Neonatal thrombocytopenia is one of the common haematological problems encountered in neonatal intensive care unit. Severe neonatal thrombocytopenia is defined as a platelet count <50×10<sup>3</sup>/µl and is relatively uncommon. Based on the time-of-onset, neonatal thrombocytopenia can be categorized into early-onset (<72 h after birth) and late-onset (>72 h after birth) thrombocytopenia. Neonatal autoimmune thrombocytopenia should be considered in any neonate who has early-onset thrombocytopenia and a maternal history of either immune thrombocytopenia (ITP) or an autoimmune disease (with or without thrombocytopenia). A term male baby, born to a 23-year-old primi-gravida with ITP was found to be thrombocytopenic at birth (platelets-85×10<sup>3</sup>/µl) without any sign of neonatal sepsis. On serial monitoring, platelet counts kept falling and on day 3, the child developed severe thrombocytopenia (platelets-6.5×10<sup>3</sup>/µl). No obvious signs of bleeding were present and the child was clinically well. Given the history of maternal thrombocytopenia (likely ITP), a possibility of neonatal autoimmune thrombocytopenia was considered. Owing to the risk of massive bleed, the baby was transfused random donor platelets and intravenous immunoglobulin (IVIg) was started on day 3. Thereafter, the platelets showed an increasing trend and child was discharged on day 7 with a platelet count of 170×10<sup>3</sup>/µl. However, on follow-up platelet count was again found to be low (84×10<sup>3</sup>/µl). It normalised subsequently, without any further requirement of IVIg. High index of suspicion, immediate work-up and diagnosis, with close monitoring and prompt management is required to prevent hemorrhagic complications in such children. Counselling for risk of thrombocytopenia in future pregnancies should be provided to parents.</p>

HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS SECONDARY TO DISSEMINATED HISTOPLASMOSIS PRESENTING AS DIFFUSE ALVEOLAR HEMORRHAGE IN A 32-YEAR-OLD WOMAN

EBV (Epstein–Barr virus) viremia causes immune dysregulation through various mechanisms, and we are understanding more that mutations in B, T, and NK (natural killer) cell signaling pathways allow EBV complications such as HLH (hemophagocytic lymphohistiocytosis) and lymphomas to arise. Here, we report a 20-year-old previously healthy, HIV- (human immunodeficiency virus-) negative male who presented with fevers, sore throat, and lymphadenopathy (LAD). He was found to have EBV viremia, pancytopenia, and elevated LFTs (liver function tests) suspicious for HLH. Bone marrow biopsy and elevated IL-2 (interleukin) receptor confirmed this diagnosis. Additionally, gastric biopsy confirmed diagnosis of plasmablastic lymphoma (PBL), a rare, aggressive HIV- and EBV-associated lymphoma. Both bone marrow and gastric biopsy showed evidence of EBV. Patients with EBV complications should have a rigorous workup to characterize the full extent of immune dysregulation including genetic testing at a high-volume center.