Clinical characteristics and immune profiles of patients with immune-mediated alopecia associated with COVID-19 vaccinations.

BACKGROUND: The clinical characteristics and pathomechanism for immune-mediated alopecia following COVID-19 vaccinations are not clearly characterized. OBJECTIVE: We investigated the causality and immune mechanism of COVID-19 vaccines-related alopecia areata (AA). STUDY DESIGN: 27 new-onset of AA patients after COVID-19 vaccinations and 106 vaccines-tolerant individuals were enrolled from multiple medical centers for analysis. RESULTS: The antinuclear antibody, total IgE, granulysin, and PARC/CCL18 as well as peripheral eosinophil count were significantly elevated in the patients with COVID-19 vaccines-related AA compared with those in the tolerant individuals (P = 2.03 × 10-5-0.039). In vitro lymphocyte activation test revealed that granulysin, granzyme B, and IFN-γ released from the T cells of COVID-19 vaccines-related AA patients could be significantly increased by COVID-19 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P = 0.002-0.04). CONCLUSIONS: Spike protein and excipients of COVID-19 vaccines could trigger T cell-mediated cytotoxicity, which contributes to the pathogenesis of immune-mediated alopecia associated with COVID-19 vaccines.

Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by SARS-CoV-2 vaccines.

Severe allergic reactions following SARS-COV-2 vaccination are generally rare, but the reactions are increasingly reported. Some patients may develop prolonged urticarial reactions following SARS-COV-2 vaccination. Herein, we investigated the risk factors and immune mechanisms for patients with SARS-COV-2 vaccines-induced immediate allergy and chronic urticaria (CU). We prospectively recruited and analyzed 129 patients with SARS-COV-2 vaccine-induced immediate allergic and urticarial reactions as well as 115 SARS-COV-2 vaccines-tolerant individuals from multiple medical centers during 2021-2022. The clinical manifestations included acute urticaria, anaphylaxis, and delayed to chronic urticaria developed after SARS-COV-2 vaccinations. The serum levels of histamine, IL-2, IL-4, IL-6, IL-8, IL-17 A, TARC, and PARC were significantly elevated in allergic patients comparing to tolerant subjects (P-values = 4.5 × 10-5-0.039). Ex vivo basophil revealed that basophils from allergic patients could be significantly activated by SARS-COV-2 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P-values from 3.5 × 10-4 to 0.043). Further BAT study stimulated by patients' autoserum showed positive in 81.3% of patients with CU induced by SARS-COV-2 vaccination (P = 4.2 × 10-13), and the reactions could be attenuated by anti-IgE antibody. Autoantibodies screening also identified the significantly increased of IgE-anti-IL-24, IgG-anti-FcεRI, IgG-anti-thyroid peroxidase (TPO), and IgG-anti-thyroid-related proteins in SARS-COV-2 vaccines-induced CU patients comparing to SARS-COV-2 vaccines-tolerant controls (P-values = 4.6 × 10-10-0.048). Some patients with SARS-COV-2 vaccines-induced recalcitrant CU patients could be successfully treated with anti-IgE therapy. In conclusion, our results revealed that multiple vaccine components, inflammatory cytokines, and autoreactive IgG/IgE antibodies contribute to SARS-COV-2 vaccine-induced immediate allergic and autoimmune urticarial reactions.

Whole genome sequencing identifies genetic variants associated with co-trimoxazole hypersensitivity in Asians.

BACKGROUND: Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole-induced SCAR remains unclear. OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR. METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia. RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1). CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.

Impact of spontaneous tumor rupture on prognosis of patients with T4 hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Compare the outcomes of three groups of patients with T4 hepatocellular carcinoma (HCC): tumor rupture with shock (RS group), tumor rupture without shock (R group), and no tumor rupture (NR group). MATERIALS AND METHODS: We retrospectively reviewed 221 patients with T4 HCC from 2010 to 2012. The clinical background and prognosis were analyzed. RESULTS: Overall in-hospital mortality rate was 18.1%; overall median survival time was 4 months. The NR group were more likely to have multiple and infiltrative tumors (P < 0.001). Relative to the NR group, the R + RS group had better survival rates at 6 months (49.2% vs. 32.2%), 1 year (35.3% vs. 21.0%), 3 years (22.5% vs. 11.0%), and 5 years (17.7% vs. 5.5%) (P = 0.010). Patients in the RS group had a higher in-hospital mortality rate, but significantly better long-term survival than the NR and R group (P < 0.001). Multivariate analysis indicated that Child-Pugh class B or C, presence of portal venous thrombosis, and absence of shock were significantly associated with poor survival. CONCLUSION: Patients with tumor rupture and shock had worse in-hospital survival. However, patients without decompensated liver cirrhosis and portal venous thrombosis, and eligible for curative treatment had favorable long-term outcome. J. Surg. Oncol. 2016;113:789-795. © 2016 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc.

Diameter change of common femoral arteries after percutaneous endovascular aortic repair with the use of the preclose technique.

OBJECTIVE: One of the major concerns regarding the preclose technique is its influence on the diameter of the accessed common femoral artery (CFA). The aim of our study was to evaluate the CFA diameter change after percutaneous endovascular aortic repair (PEVAR) with the use of the preclose technique. METHODS: From February 2012 to September 2013, 192 patients who underwent PEVAR with the preclose technique were reviewed. The patients were followed postoperatively with computed tomographic angiography 1, 6, and 12 months after PEVAR, and only those with complete computed tomography studies were included. For each access site, the inner diameter (ID) and outer diameter (OD) of the CFA were measured, and the diameters at various time periods were compared. In addition, the patient cohort was divided into four subgroups according to two parameters: the sheath size (12-16F and 18-24F) and the number of closure devices used for the preclose technique (two devices, more than two devices). The differences in diameter change between the subgroups were analyzed. The significance of the diameter change and the influences of the two parameters were analyzed statistically with the use of the paired t-test, one-way analysis of variance, and two-way analysis of variance. RESULTS: Fifty-eight patients fulfilled the study criteria. No significant influence on the ID of the accessed CFAs was observed at baseline and 1, 6, and 12 months (9.0 ± 1.75 mm, 9.1 ± 1.70 mm, 8.9 ± 1.72 mm, and 9.0 ± 1.68 mm, respectively). By contrast, a significant increase in initial OD occurred 1 month after PEVAR but gradually decreased in size in the following 11 months (13.0 ± 2.37 mm, 16.4 ± 3.44 mm, 14.2 ± 3.06 mm, and 13.5 ± 2.42 mm, respectively). Both the sheath size and the number of closure devices significantly affected the OD change (P < .001 and P = .037, respectively). The effect produced by the number of closure devices extended to 6 months after PEVAR, but the effect of the sheath size ceased before that time. CONCLUSIONS: This study demonstrates that PEVAR with the use of the preclose technique does not influence the ID of the accessed CFA, whereas the OD changes gradually over 1 year. These results may indicate that future endovascular interventions can be performed with the use of the same access without the risk of vascular narrowing.

The Function of HLA-B*13:01 Involved in the Pathomechanism of Dapsone-Induced Severe Cutaneous Adverse Reactions.

Dapsone-induced hypersensitivity reactions may cause severe cutaneous adverse reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS). It has been reported that HLA-B*13:01 is strongly associated with dapsone-induced hypersensitivity reactions among leprosy patients. However, the phenotype specificity and detailed immune mechanism of HLA-B*13:01 remain unclear. We investigated the genetic predisposition, HLA-B*13:01 function, and cytotoxic T cells involved in the pathogenesis of dapsone-induced severe cutaneous adverse reactions. We enrolled patients from Taiwan and Malaysia with DRESS and maculopapular eruption with chronic inflammatory dermatoses. Our results showed that the HLA-B*13:01 allele was present in 85.7% (6/7) of patients with dapsone DRESS (odds ratio = 49.64, 95% confidence interval = 5.89-418.13; corrected P = 2.92 × 10-4) but in only 10.8% (73/677) of general population control individuals in Taiwan. The level of granulysin, the severe cutaneous adverse reaction-specific cytotoxic protein released from cytotoxic T cells, was increased in both the plasma of DRESS patients (36.14 ± 9.02 ng/ml, P < 0.05) and in vitro lymphocyte activation test (71.4%, 5/7 patients) compared with healthy control individuals. Furthermore, dapsone-specific cytotoxic T cells were significantly activated when co-cultured with HLA-B*13:01-expressing antigen presenting cells in the presence of dapsone (3.9-fold increase, compared with cells with no HLA-B*13:01 expression; P < 0.01). This study indicates that HLA-B*13:01 is strongly associated with dapsone DRESS and describes a functional role for the HLA-restricted immune mechanism induced by dapsone.

Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions.

BACKGROUND: Cytotoxic T lymphocyte-mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. METHODS: We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. RESULTS: Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%-62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. CONCLUSIONS: The anti-TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01276314. FUNDING: Ministry of Science and Technology of Taiwan.

The clinicopathological features of sinonasal angiomatous polyps.

BACKGROUND: Sinonasal angiomatous polyp (SAP) is a rare subtype of sinonasal polyp that might be misdiagnosed as a malignant lesion due to its clinical symptoms. METHODS: We retrospectively enrolled the patients who were diagnosed with SAP in our hospital during 2008-2015. We analyzed the clinical symptoms, radiological findings, and pathological features of all patients diagnosed with SAP. RESULTS: Unilateral nasal obstruction, rhinorrhea, and epistaxis were the common symptoms. SAPs all originated from maxillary sinus and extended to nasal cavity with or without involving the nasopharynx. Expansile mass with surrounding bony destruction is typical on computed tomography imaging but specific for SAPs. The magnetic resonance revealed high signal intensity on T1-weighted images and hypointense rim on T2-weighted images. CONCLUSION: Computed tomography and magnetic resonance together might give rise to more accurate diagnosis of SAP. Incisional biopsy does help if the clinician suspects a malignant lesion. To treat SAP, complete removal is the optimal choice.

Performance of adaptive iterative dose reduction 3D integrated with automatic tube current modulation in radiation dose and image noise reduction compared with filtered-back projection for 80-kVp abdominal CT: Anthropomorphic phantom and patient study.

OBJECTIVES: Evaluate the performance of Adaptive Iterative Dose Reduction 3D (AIDR 3D) and compare with filtered-back projection (FBP) regarding radiation dosage and image quality for an 80-kVp abdominal CT. MATERIALS AND METHODS: An abdominal phantom underwent four CT acquisitions and reconstruction algorithms (FBP; AIDR 3D mild, standard and strong). Sixty-three patients underwent unenhanced liver CT with FBP and standard level AIDR 3D. Further post-acquisition reconstruction with strong level AIDR 3D was made. Patients were divided into two groups (< and ≧29cm) based on the abdominal effective diameter (Deff) at T12 level. Quantitative (attenuation, noise, and signal-to-noise ratio) and qualitative (image quality, noise, sharpness, and artifact) analysis by two readers were assessed and the interobserver agreement was calculated. RESULTS: Strong level AIDR 3D reduced radiation dose by 72% in the phantom and 47.1% in the patient study compared with FBP. There was no difference in mean attenuations. Image noise was the lowest and signal-to-noise ratio the highest using strong level AIDR 3D in both patient groups. For Deff<29cm, image sharpness of FBP was significantly different from those of AIDR 3D (P<0.05). For Deff ≧29cm, image quality of AIDR 3D was significantly more favorable than FBP (P<0.05). Interobserver agreement was substantial. CONCLUSIONS: Integrated AIDR 3D allows for an automatic reduction in radiation dose and maintenance of image quality compared with FBP. Using AIDR 3D reconstruction, patients with larger abdomen circumference could be imaged at 80kVp.

Liver metastasis from hepatoid adenocarcinoma of the stomach mimicking hepatocellular carcinoma: Dynamic computed tomography findings.

AIM: To evaluate the dynamic computed tomography (CT) findings of liver metastasis from hepatoid adenocarcinoma of the stomach (HAS) and compared them with hepatocellular carcinoma (HCC). METHODS: Between January 2000 and January 2015, 8 patients with pathologically proven HAS and liver metastases were enrolled. Basic tumor status was evaluated for the primary tumor location and metastatic sites. The CT findings of the liver metastases were analyzed for tumor number and size, presence of tumor necrosis, hemorrhage, venous tumor thrombosis, and dynamic enhancing pattern. RESULTS: The body and antrum were the most common site for primary HAS (n = 7), and observed metastatic sites included the liver (n = 8), lymph nodes (n = 7), peritoneum (n = 4), and lung (n = 2). Most of the liver metastases exhibited tumor necrosis regardless of tumor size. By contrast, tumor hemorrhage was observed only in liver lesions larger than 5 cm (n = 4). Three patterns of venous tumor thrombosis were identified: direct venous invasion by the primary HAS (n = 1), direct venous invasion by the liver metastases (n = 7), and isolated portal vein tumor thrombosis (n = 2). Dynamic CT revealed arterial hyperattenuation and late phase washout in all the liver metastases. CONCLUSION: On dynamic CT, liver metastasis from HAS shared many imaging similarities with HCC. For liver nodules, the presence of isolated portal vein tumor thrombosis and a tendency for tumor necrosis are imaging clues that suggest the diagnosis of HAS.

Kimura's disease: clinical and imaging parameters for the prediction of disease recurrence.

Kimura's disease is a rare chronic inflammatory disorder with a high rate of recurrence. The clinical and imaging features of Kimura's disease have been documented in the literature, but the relationship between these features and disease recurrence is still unclear. We conclude that disease duration of greater than 5 years, bilateral involvement, a lesion diameter of greater than 3 cm, a blood eosinophil count greater than 20%, and ill-defined lesions are predictive factors for the recurrence of Kimura's disease.