Clinical and histopathological spectrum of delayed adverse cutaneous reactions following COVID-19 vaccination.

BACKGROUND: As more people become vaccinated against the SARS-CoV-2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. METHODS: In this IRB-approved retrospective case series, biopsy specimens of potential cutaneous adverse reactions from the Pfizer-BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. RESULTS: Twelve cases were included. Histopathological features from two injection-site reactions showed a mixed-cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsy specimens came from generalized eruptions that showed interface changes consistent with an exanthematous drug reaction. Three biopsy specimens revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small-vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new-onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. CONCLUSIONS: Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA-based COVID-19 vaccines. Histopathological patterns include mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune-mediated cutaneous presentations such as vasculitis or bullous pemphigoid.

Association between Itch and Cancer in 3836 Pediatric Pruritus Patients at a Tertiary Care Center.

Background: Pruritus is a well-recognized paraneoplastic phenomenon. Previous studies have examined the association of itch with a variety of malignancies in adults. However, no large study has examined this association in a pediatric population. Methods: A retrospective study was conducted of patients age 18 or less seen at Johns Hopkins Health System between 2012 and 2019. Results: A pediatric hospital population of 1,042,976 patients was reviewed. Pruritus was observed in 3836 pediatric patients of whom 130 also had cancer. Pediatric patients with pruritus were significantly more likely to have concomitant malignancy compared to pediatric patients without pruritus (OR 12.84; 95% CI 10.73-15.35, p < 0.001). Malignancies most strongly associated with pruritus included neoplasms of the blood (OR 14.38; 95% CI 11.30-18.29, p < 0.001), bone (OR 29.02, 95% CI 18.28-46.06, p < 0.001) and skin (OR 22.76, 95% CI 9.14-56.72, p < 0.001. Conclusions: Pruritus is significantly associated with malignancy in the pediatric hospital population. Clinicians should also be aware of the high burden of itch in pediatric malignancies and the variation in pruritus across malignancies.

One hertz versus ten hertz repetitive TMS treatment of PTSD: A randomized clinical trial.

The purpose of this trial was to test whether right prefrontal cortex 1 Hz versus 10 Hz rTMS provides a significantly greater improvement in PTSD symptoms and/or function. Veterans 18 to 50 years of age suffering from PTSD were randomized to right prefrontal 1 Hz rTMS [2400 pulses/session] versus right prefrontal 10 Hz rTMS [2400 pulses/session]. The treatments were performed 5 days a week for 6 weeks with a 3-week taper using the NeuroStar system. There were one month and three months post treatment follow-up evaluations. Forty-four participants were enrolled with 17 being randomized to 1 Hz rTMS and 18 to 10 Hz rTMS. Both groups had significant improvement in PTSD and depression scores from baseline to the end of acute treatment. The 10 Hz group but not the 1 Hz group demonstrated significant improvement in function. Although both groups demonstrated significant improvement in PTSD and depression symptoms, a significant advantage for either the 1 Hz or 10 Hz frequency group on any of the scales acquired was not demonstrated. Further work is required with larger samples sizes to test whether low or high frequency is superior or if individual differences would indicate the more effective frequency.

Association between itch and cancer in 16,925 patients with pruritus: Experience at a tertiary care center.

BACKGROUND: Pruritus has been associated with cancer. However, limited data are available on the types of underlying malignancies associated with pruritus. OBJECTIVE: We sought to characterize the association between pruritus and different cancer types, as well as variations by racial group. METHODS: Cross-sectional study of patients ≥18 years of age seen at the Johns Hopkins Health System during 2013-2017. Patients with pruritus were compared with patients without pruritus. Analyses were stratified by race. RESULTS: Patients with pruritus were more likely to have concomitant malignancy than those without pruritus (odds ratio 5.76, 95% confidence interval 5.53-6.00). Most strongly associated were cancers of the liver, gallbladder and biliary tract, hematopoietic system, and skin. Compared with white patients, black patients more frequently had soft tissue, dermatologic, and hematologic malignancies and less frequently had liver, respiratory, gastrointestinal, and gynecologic malignancies. LIMITATIONS: The cross-sectional design precludes analysis of the temporal association between pruritus and malignancy. The study is limited to a single tertiary care center. CONCLUSION: Pruritus is most strongly associated with cancers of the liver, skin, and hematopoietic system. Black patients with pruritus have a higher likelihood of skin, soft tissue, and hematologic malignancies than white patients, while whites have higher likelihoods of liver, respiratory, gastrointestinal, and gynecologic malignancies.

Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility.

The inwardly rectifying K+ channel Kir4.1 is broadly expressed by CNS glia and deficits in Kir4.1 lead to seizures and myelin vacuolization. However, the role of oligodendrocyte Kir4.1 channels in controlling myelination and K+ clearance in white matter has not been defined. Here, we show that selective deletion of Kir4.1 from oligodendrocyte progenitors (OPCs) or mature oligodendrocytes did not impair their development or disrupt the structure of myelin. However, mice lacking oligodendrocyte Kir4.1 channels exhibited profound functional impairments, including slower clearance of extracellular K+ and delayed recovery of axons from repetitive stimulation in white matter, as well as spontaneous seizures, a lower seizure threshold, and activity-dependent motor deficits. These results indicate that Kir4.1 channels in oligodendrocytes play an important role in extracellular K+ homeostasis in white matter, and that selective loss of this channel from oligodendrocytes is sufficient to impair K+ clearance and promote seizures.

Novel mutation in the KCNJ10 gene in three siblings with seizures, ataxia and no electrolyte abnormalities.

We report a consanguineous family with three affected siblings with novel mutation in the KCNJ10 gene. All three presented with central nervous system symptoms in the form of infantile focal seizures, ataxia, slurred speech with early developmental delay and intellectual disability in two siblings. None had any associated electrolyte abnormalities and no symptomatic hearing deficits were observed.

Electrophysiological properties of NG2(+) cells: Matching physiological studies with gene expression profiles.

NG2(+) glial cells are a dynamic population of non-neuronal cells that give rise to myelinating oligodendrocytes in the central nervous system. These cells express numerous ion channels and neurotransmitter receptors, which endow them with a complex electrophysiological profile that is unique among glial cells. Despite extensive analysis of the electrophysiological properties of these cells, relatively little was known about the molecular identity of the channels and receptors that they express. The generation of new RNA-Seq datasets for NG2(+) cells has provided the means to explore how distinct genes contribute to the physiological properties of these progenitors. In this review, we systematically compare the results obtained through RNA-Seq transcriptional analysis of purified NG2(+) cells to previous physiological and molecular studies of these cells to define the complement of ion channels and neurotransmitter receptors expressed by NG2(+) cells in the mammalian brain and discuss the potential significance of the unique physiological properties of these cells. This article is part of a Special Issue entitled SI:NG2-glia(Invited only).