A case of Schnitzler syndrome with unusual immunoglobulin A gammopathy exacerbated by COVID-19 infection.

Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by chronic urticarial rash and monoclonal immunoglobulin M (IgM) or IgG gammopathy. Viruses, including COVID-19, activate the innate immune system, therefore SchS, in which the innate immune system is improperly activated, is hypothesized to be exacerbated by viral infection. However, there were no reported SchS cases exacerbated by any viral infection. Here, we report a SchS case with an unusual IgA gammopathy manifested and exacerbated by COVID-19 infection. This report advocates the need for recognizing unusual cases of SchS with monoclonal IgA, and following up on paraprotein like IgA even when it is initially undetectable in cases with SchS symptoms. We also hypothesize that existing autoinflammatory diseases may be exacerbated by COVID-19 infection in the case of a combination of these diseases.

Polypoid Malignant Melanoma with Spontaneous Decapitation Showing Favorable Prognosis: A Case Report.

Introduction: Regression of malignant melanoma (MM) is a commonly observed phenomenon, which refers to disappearance or loss of all or part of MM. It can be identified both clinically and histologically, and high probability of histological regression of MM (10-58%) has been reported. However, the decapitation of skin tumor has rarely been described in the English literature, and decapitation in MM has not been reported. Here, we report the case of polypoid MM with spontaneous decapitation. Case Presentation: An 81-year-old Japanese woman was referred to our hospital due to a polypoid nodule on her cheek. She was diagnosed with MM at stage IIC (T4bN0M0) by histological examinations. Three weeks after the biopsy, the nodule decapitated spontaneously without bleeding, and an ulcer developed on the base of the polypoid nodule. The histological examination of the additionally resected ulcerative lesion under the nodule revealed infiltration of T cells mainly composed of CD8⁺ natural killer T cells. No recurrence or metastasis has been observed for 4 years. Conclusion: This is the first case report of polypoid MM with spontaneous decapitation, which may be attributed to natural killer T cells. Moreover, this case shows favorable prognosis, while it is said that the regression in thick MM does not have prognostic advantage and polypoid topography has been reported to be related to extremely poor prognosis. Further investigations are needed to evaluate the prognostic advantage of decapitation in MM and other skin tumors.

Exploratory study on quantitative assessment of skin hardness in patients with systemic sclerosis using SOFTGRAM.

OBJECTIVES: There is a lack of quantitative and objective methods for measuring skin hardness. This study aimed to verify whether SOFTGRAM, a device that can measure elastic modulus using the Hertz elastic contact theory, could be used to evaluate skin hardness in systemic sclerosis (SSc). METHODS: Skin score according to the modified Rodnan total skin thickness score and elastic modulus of the skin using SOFTGRAM were measured for 20 patients with SSc and 20 healthy controls on 8 parts of the body, both of the cheeks, forearms, fingers, and hands. Five observers shared to measure skin score 320 times (40 participants × 8 parts). Elastic modulus was measured 1600 times (40 participants × 8 parts × 5 times each). As an additional examination to compare differences between observers, the skin score of another healthy control was measured 40 times (5 observers × 8 parts). Elastic modulus was measured 200 times (5 observers × 8 parts × 5 times each). RESULTS: There was a significant correlation between elastic modulus and skin score (correlation coefficient=0.67, p<0.001) and a significant difference in elastic modulus (8 parts: healthy controls vs. limited cutaneous SSc vs. diffuse cutaneous SSc: 22.6±15.7 vs. 32.0±27.7 vs. 44.8±39.8, p<0.001). Intraobserver reliabilities were sufficient in 6 out of 7 observers; however, interobserver was less satisfactory. CONCLUSIONS: This study showed the practicality of SOFTGRAM as an accurate measurement method of skin hardness but also revealed points to be improved. More studies are needed to find an accurate measurement method of skin hardness.

Efficacy of salvage therapies for advanced acral melanoma after anti-PD-1 monotherapy failure: a multicenter retrospective study of 108 Japanese patients.

Background: Anti-programmed cell death protein 1 (PD-1) monotherapy is one of the standard systemic therapies for advanced melanoma; however, the efficacy of salvage systemic therapies after PD-1 monotherapy failure (PD-1 MF), particularly in acral melanoma (AM), the main clinical melanoma type in Japanese patients, is unclear. This study aimed to investigate the efficacy of salvage systemic therapies in Japanese patients with AM after PD-1 MF. Patients and methods: The study included 108 patients with advanced AM (palm and sole, 72; nail apparatus, 36) who underwent salvage systemic therapy at 24 Japanese institutions. We mainly assessed the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Thirty-six (33%) patients received ipilimumab, 23 (21%) received nivolumab and ipilimumab (nivo/ipi), 10 (9%) received cytotoxic chemotherapy, 4 (4%) received BRAF and MEK inhibitors (BRAFi/MEKi), and the remaining 35 (32%) continued with PD-1 monotherapy after disease progression. The ORRs in the ipilimumab, nivo/ipi, cytotoxic chemotherapy, and BRAFi/MEKi groups were 8, 17, 0, and 100%, respectively. The nivo/ipi group showed the longest OS (median, 18.9 months); however, differences in ORR, PFS, and OS between the groups were insignificant. The OS in the nivo/ipi group was higher in the palm and sole groups than in the nail apparatus group (median: not reached vs. 8.7 months, p < 0.001). Cox multivariate analysis demonstrated that nail apparatus melanoma independently predicted unfavorable PFS and OS (p = 0.006 and 0.001). The total OS (from PD-1 monotherapy initiation to death/last follow-up) was insignificant between the groups. Conclusion: Nivo/ipi was not more effective than cytotoxic chemotherapy and ipilimumab after PD-1 MF in patients with advanced AM. The prognosis after PD-1 MF would be poorer for nail apparatus melanoma than for palm and sole melanoma.

Analysis of IL-10 and IL-35 in dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid.

The association between immunoregulatory cytokines, such as interleukin (IL)-10 or IL-35, and dipeptidyl peptidase-4 inhibitor (DPP4i)-related bullous pemphigoid (BP) has not been evaluated. Serum IL-10 and IL-35 levels were measured in 39 patients with BP (24 males and 15 females; 6 DPP4i-related and 33 DPP4i-unrelated BP patients) and 10 healthy controls. The number of CD26+ cells in the dermis around bulla on sections was counted immunohistochemically for 12 patients (six patients with DPP4i-related BP and six randomly sampled patients with DPP4i-unrelated BP). Patients with DPP4i-related BP had lower levels of serum eosinophils (DPP4i-related vs. DPP4i-unrelated BP: 476.1 ± 234.0 vs. 911.3 ± 948.8/µL; p = 0.537) and a higher rate of infiltrating CD26+ cells (32.9 ± 7.1% vs. 15.7 ± 4.4%; p = 0.01). There were no significant differences in serum IL-10 (6.77 ± 0.24 vs. 6.84 ± 0.20 pg/mL), serum IL-35 (2.63 ± 0.17 vs. 2.63 ± 0.21 pg/mL), serum anti-BP180NC16a antibodies (67.31 ± 37.4 vs. 76.18 ± 54.59 U/mL) and Bullous Pemphigoid Disease Area Index before treatment in this study. Serum IL-10 and IL-35 levels do not increase in patients with BP and may not be a candidate for a therapeutic target for BP. An increase in CD26+ cells might be associated with DPP4i-related BP.

Evaluation of prognostic prediction ability of the novel Japanese risk factor scoring system in a Japanese cohort of resectable cutaneous squamous cell carcinoma: A retrospective cross-sectional study.

Japanese patients with very high-risk cutaneous squamous cell carcinomas (cSCCs), based on the National Comprehensive Cancer Network guidelines, have been reported to display a higher cumulative incidence of relapse and disease-specific death (DSD) than those with high-risk cSCC. Therefore, prognosis prediction is crucial for Japanese patients with very high-risk cSCCs. Herein, we aimed to evaluate the prognostic prediction ability of our novel Japanese Risk Factor Scoring Systems (JARF scoring) in a Japanese cohort of cSSC patients. Data of 424 Japanese patients with resectable very high-risk cSCCs were analysed. We compared the prognostic ability of the following three staging systems: Brigham and Women's Hospital (BWH) tumour staging, number of NCCN very high-risk factors, and JARF scoring, including recurrent tumour, high-risk histological features, deep tumour invasion and lymphatic or vascular involvement as risk factors. The prognostic ability of these staging systems was evaluated according to the cumulative incidence of local recurrence (LR), regional lymph node metastasis (RLNM), DSD, and overall survival (OS). When BWH staging was used, high T stage led to significantly poor outcomes only in the cumulative incidence of RLNM (p = 0.01). The presence of very high-risk NCCN factors led to significantly poor outcomes in terms of RLNM (p = 0.03) and OS (p = 0.02). Meanwhile, a high number of risk factors in the JARF scoring system clearly led to poor outcomes in terms of LR (p = 0.01), RLNM (p < 0.01), DSD (p = 0.03), and OS (p < 0.01). The JARF scoring system may accurately predict the risk of recurrence and death in very high-risk cSCC patients in Japan.