Is There a Correlation Between Immune Thrombocytopenia and Immunoglobulin G4-Related Disease?

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition causing organ swelling and fibrosis. Rarely, it coexists with primary immune thrombocytopenia (ITP), characterized by low platelet count (< 100 × 106/L) without an underlying cause. We present a case of a 56-year-old woman diagnosed with ITP in 2005, successfully treated with dexamethasone and intravenous immunoglobulins (IVIG). In 2011, she was diagnosed with IgG4-RD, type I autoimmune pancreatitis, initially treated with steroids then azathioprine with no response. ITP relapses were managed with prednisone/IVIG, rituximab, and thrombopoietin-receptor agonist therapy. Fostamatinib provided temporary relief, but platelet count dropped again in 2023. Combination therapy with small doses of prednisone and mycophenolate showed a partial response, maintaining platelet count over 50 × 106/L. Further investigation is warranted to explore any correlation between these two conditions, especially considering the patient's prolonged response to immunosuppressors.

Uncommon Presentation of Sarcoidosis with Severe Thrombocytopenia and Hemorrhagic Diathesis.

Sarcoidosis, a multi-organ system disease, often presents insidiously. Thrombocytopenia in sarcoidosis is frequent because of hypersplenism, granulomas infiltrating the bone marrow, or immune thrombocytopenia (ITP). The diagnosis of ITP relies on exclusionary criteria, given the absence of a definitive laboratory diagnostic feature. In the era prior to modern ITP management, sarcoidosis-associated ITP was known to manifest severely, often showing resistance to treatment and an increased risk of mortality. In this case, we present a young male who was admitted to a district hospital's emergency room, displaying symptoms of hematuria, gingival bleeding, and a petechial rash. Blood tests revealed severe thrombocytopenia with a platelet count of 0, while all other metabolic and serological exams returned normal results. Infectious and autoimmune causes were ruled out, and a bone marrow examination excluded any hematological disorder. Initial management, including platelet transfusion and presumptive treatment for ITP with dexamethasone and Human Immunoglobulin IV (IVIG), failed to improve the patient's platelet count or alleviate the hemorrhagic diathesis. Second-line therapy with Rituximab and Methylprednisolone was initiated with no benefit. Considering the hemorrhagic signs and the delayed response of Rituximab, we shifted to third-line therapy with Romiplostim at the maximal dose and continued Methylprednisolone. The platelet count recovered completely after the second Romiplostim administration (over 350 × 109 platelets/L) and Methylprednisolone was rapidly tapered. To further study the causes of thrombocytopenia a total body CT scan was performed and it identified non-homogeneously hypodense tissue in the bilateral hilar area extending medially to the subcarinal area, suggesting possible lymphatic origin and raising suspicion of sarcoidosis. Further investigations, including Angiotensin Converting Enzyme (ACE) titration, bronchoscopy, bronchoalveolar lavage, and EndoBronchial UltraSound-guided TransBronchial Needle Aspiration (EBUS-TBNA), confirmed the diagnosis of sarcoidosis. Despite a mild restrictive insufficiency noted in spirometry, the patient remained asymptomatic with only a mild respiratory insufficiency, and hence, was enlisted for follow-up. As for the ITP, the platelet count remained normal over a year. Notably, while sarcoidosis onset often predates ITP onset by an average of 48 months, in our case the onset of the two diseases was simultaneously. Our case adds valuable information to the limited body of knowledge regarding the treatment of sarcoidosis-associated ITP.

A rare case of aCML associated with CNS involvement and with aggressive clinical course.

The presence of neutrophilic leukocytosis may underlie a wide variety of diseases. Some rare causes of neutrophilia might be chronic neutrophilic leukemia (CNL) and myelodysplastic/myeloproliferative neoplasm with neutrophilia (MDS with neutrophilia). Here we report a case of a 78-year-old woman who came to our ER due to severe leukocytosis and anemia on a routine check-up. The patient was asymptomatic and the last exams available showed a mild leukopenia and thrombocytopenia. The abdominal echography showed mild splenomegaly The patient underwent bone marrow (BM) examinations. One week later, the patient presented mental deterioration. The patient underwent a cranial CT and RMN that showed multiple lesions of 11 mm in the brain parenchyma, cerebellum and encephalic trunk. Another week later, the clinical presentations worsened: she was in a comatous state and feverish 40 °C unresponsive to steroid therapy. Autopsy showed a leukemic and hemorrhage infiltration in multiple organs and in the BM a cellularity of 100% represented by myeloid elements with a slowdown maturation with blasts 5%. According to WHO 2016 this case can be reported as an aCML, an MDS/MPN overlap syndrome that is difficult to differentiate from a CNL.

Bcl-xL represents a therapeutic target in Philadelphia negative myeloproliferative neoplasms.

Myeloproliferative neoplasms are divided into essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Although ruxolitinib was proven to be effective in reducing symptoms, patients rarely achieve complete molecular remission. Therefore, it is relevant to identify new therapeutic targets to improve the clinical outcome of patients. Bcl-xL protein, the long isoform encoded by alternative splicing of the Bcl-x gene, acts as an anti-apoptotic regulator. Our study investigated the role of Bcl-xL as a marker of severity of MPN and the possibility to target Bcl-xL in patients. 129 MPN patients and 21 healthy patients were enrolled in the study. We analysed Bcl-xL expression in leucocytes and in enriched CD34+ and CD235a+ cells. Furthermore, ABT-737, a Bcl-xL inhibitor, was tested in HEL cells and in leucocytes from MPN patients. Bcl-xL was found progressively over-expressed in cells from ET, PV and PMF patients, independently by JAK2 mutational status. Moreover, our data indicated that the combination of ABT-737 and ruxolitinib resulted in a significantly higher apoptotic rate than the individual drug. Our study suggests that Bcl-xL plays an important role in MPN independently from JAK2 V617F mutation. Furthermore, data demonstrate that targeting simultaneously JAK2 and Bcl-xL might represent an interesting new approach.