Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency.

Immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines in primary antibody deficiencies (PADs) are largely unknown. We investigated antibody and CD4+ T-cell responses specific for SARS-CoV-2 spike protein (S) before and after vaccination and associations between vaccine response and patients' clinical and immunological characteristics in PADs. The PAD cohort consisted of common variable immune deficiency (CVID) and other PADs, not meeting the criteria for CVID diagnosis (oPADs). Anti-S IgG, IgA, and IgG subclasses 1 and 3 increased after vaccination and correlated with neutralization activity in HCs and patients with oPADs. However, 42% of CVID patients developed such responses after the 2nd dose. A similar pattern was also observed with S-specific CD4+ T-cells as determined by OX40 and 4-1BB expression. Patients with poor anti-S IgG response had significantly lower levels of baseline IgG, IgA, CD19+ B-cells, switched memory B-cells, naïve CD8+ T-cells, and a higher frequency of EM CD8+ T-cells and autoimmunity compared to patients with adequate anti-S IgG responses. Patients with oPADs can develop humoral and cellular immune responses to vaccines similar to HCs. However, a subset of CVID patients exhibit impairment in developing such responses, which can be predicted by the baseline immune profile and history of autoimmunity.

Bullous hemorrhagic dermatosis is an under-recognized side effect of full dose low-molecular weight heparin: a case report and review of the literature.

Bullous hemorrhagic dermatosis (BHD) is a systemic side-effect of low molecular weight heparin, characterized by multiple intra-epidermal hemorrhages distant from the site of injection. There have been several small case series and literature reviews on BHD, but none have captured a complete set of reported patients. We sought to describe a case of BHD with late diagnosis and completely summarize the existing English and Spanish literature with searches of Pubmed, Scopus, Ovid Embase and Ovid Medline. After narrowing to 33 relevant reports, we describe 90 reported cases worldwide from 2004 to 2017, in addition to a new case from our institution as a means of comparison. We found that BHD was common in elderly men (mean age 72 ± 12; male:female, 1.9:1) and typically occurred within 7 days of administration of anticoagulation (median 7 days ± 6.4) usually with enoxaparin use (66% of cases). Lesions occurred primarily on the extremities only (67.9% of cases). Coagulation testing was most often normal before administration, and the majority of patients had coagulation testing in therapeutic range during treatment. Most practitioners stopped anticoagulation if continued therapeutic intervention was no longer required (57% of cases), or changed therapy to another anticoagulation if continued treatment was required (14.3% of cases). Therapy was continued outright in 23% of patients. The lesions usually resolved within 2 weeks (mean days, 13.0 ± 7.4). There was no difference in time to resolution between patients who continued the culprit anticoagulant or changed to a different anticoagulant, and those who discontinued anticoagulation altogether (13.9 days vs. 12.1, p = 0.49). Four deaths have been reported in this clinical context, two specified as intracranial hemorrhage. These deaths were unrelated to the occurrence of BHD. Continuation of low-molecular weight heparins appeared to be safe in patients with BHD.

A rare case of visceral leishmaniasis in an immunocompetent traveler returning to the United States from Europe.

A young, healthy traveler returning to the United States presented with fever, night sweats, splenomegaly, and pancytopenia. Bone marrow biopsy revealed leishmaniasis (Leishmania infantum), likely acquired in southern France. Although many cases of endemic visceral leishmaniasis (VL) have been reported in Europe, this is a rare case of imported VL in a healthy traveler returning from Europe to the US. Despite successful initial treatment with liposomal amphotericin B (LamB), relapse occurred. Treatments for VL in immunocompetent individuals are highly effective, but relapse can occur. There is more extensive experience in endemic areas with treating relapse that may be lacking in North America. This case alerts physicians in the US that immunocompetent adults can acquire VL during brief visits to endemic areas in Europe. It is important that travelers be counseled on preventive measures. Patients should be monitored after treatment for relapse.

Core biopsies of the breast: diagnostic pitfalls.

The incidence of breast cancer is increasing worldwide. In this review article, the authors compare and contrast the incidence of breast cancer, and the inherent differences in the United States (US) and India in screening techniques used for diagnosing breast cancer. In spite of these differences, core biopsies of the breast are common for diagnosis of breast cancer in both countries. The authors describe "Best Practices" in the reporting and processing of core biopsies and in the analysis of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor Receptor 2 (Her2/neu). The pitfalls in the diagnosis of fibroepithelial lesions of the breast on core biopsy are discussed, as also the significance of pseudoangiomatous stromal hyperplasia of the breast (PASH) is discussed in core biopsy. In this review, the management and diagnosis of flat epithelial atypia and radiation atypia are elaborated and the use of immunohistochemistry (IHC) in papillary lesions, phyllodes tumor, and complex sclerosing lesions (radial scars) is illustrated. Rarer lesions such as mucinous and histiocytoid carcinoma are also discussed.