IMPORTANCE: De novo bullous pemphigoid (BP) is a rare immune-mediated adverse event from immune checkpoint inhibitors (ICIs) that can necessitate permanent discontinuation of the anticancer therapy, ...but the risk factors for developing this toxic effect are unknown. OBJECTIVE: To compare potential risk factors for BP in patients treated with ICIs who did and did not develop BP. DESIGN, SETTING, AND PARTICIPANTS: This cohort and nested propensity score–matched case-control study was conducted at the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Massachusetts General Hospital. All patients at these facilities with de novo BP after ICI treatment were compared with all patients on the cancer registry who were treated with ICIs between October 1, 2014, and December 31, 2020. Patients with incomplete or blinded data regarding the ICI agent or total cycles were excluded. EXPOSURES: In the cohort, assessed potential risk factors included age at ICI introduction, sex, ICI molecular target, and cancer type, which were then used as matching variables. In the propensity score–matched case-control analysis, risk factors assessed included sex, race and ethnicity, cancer stage, metastasis sites, idiopathic BP comorbidities, pre–ICI vaccination, radiation history, body mass index, and derived neutrophil-to-lymphocyte ratio. MAIN OUTCOMES AND MEASURES: Diagnosis of BP at any point after ICI treatment, confirmed by direct immunofluorescence, indirect immunofluorescence, autoantibody serologies, or diagnostic consensus among study board-certified dermatologists. Odds ratios (ORs) and 95% CIs were calculated for all risk factors. In the secondary analysis, best overall responses to ICIs between cases and controls were compared by Fisher exact test. RESULTS: Among 5636 patients treated with ICIs at Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Massachusetts General Hospital during the study period, 35 (0.6%; median IQR age, 72.8 13.4 years; 71.4% 25 male patients) developed BP. In a multivariate logistic regression model that assessed 2955 patients with complete data in the cancer registry, age 70 years or older (OR, 2.32; 95% CI, 1.19-4.59; P = .01), having melanoma (OR, 3.21; 95% CI, 1.51-6.58; P < .003), and having nonmelanoma skin cancer (OR, 8.32; 95% CI, 2.81-21.13; P < .001) were significantly associated with developing BP. In the nested 1:2 case-control comparison of all 35 cases to 70 propensity score–matched controls, a complete or partial response on initial restaging imaging was a risk factor for BP development (OR, 3.37; 95% CI, 1.35-9.30; P = .01). Bullous pemphigoid cases also more frequently exhibited overall tumor response to ICIs than matched controls (29 of 35 82.9% vs 43 of 70 61.4%; P = .03). CONCLUSIONS AND RELEVANCE: In this cohort study, age 70 years or older and skin cancer were associated with increased risk of developing ICI-associated BP. Given the association of BP with improved initial and best overall tumor responses, early identification and toxic effect–directed treatment should be prioritized, especially in individuals at risk for developing de novo BP.
Immune checkpoint inhibition (ICI) can induce progression of pre-existing radiation-induced morphoea beyond the irradiated field and into deeper structures including the muscle and fascia. Dupilumab, ...an interleukin-4 receptor antagonist, should be considered in patients with refractory radiation or ICI-induced morphoea and may allow for continued anticancer treatment.
Introduction:
Linear morphea is an inflammatory condition that is often treated with systemic glucocorticoids and methotrexate, with mycophenolate mofetil being used as an alternative agent. However, ...there are few published reports on beneficial effect of abatacept for refractory disease. We present a case of a woman in her 30s who presented with linear morphea on her scalp, with a notable response following the addition of subcutaneous abatacept.
Methods:
Computational analysis was performed comparing the immune cell scores of skin biopsies from five morphea skin biopsies from three additional unique patients and 15 healthy control skin biopsies. Value of p < 0.05 was considered statistically significant.
Results:
Immune cell scores demonstrated a statistically significant enrichment of activated CD4 memory T cells, M1 macrophages, monocytes, and memory B cells comparing skin biopsies of morphea versus healthy controls (p < 0.05 for all).
Discussion:
Abatacept may be considered for recalcitrant cases of morphea. Our computational analysis supports a well-designed study is needed to assess abatacept as first-line therapy.
BACKGROUND:Computed tomographic angiography is increasingly used during surgical planning for abdominally based microvascular breast reconstruction. Cost-analysis studies have demonstrated a benefit ...to the use of computed tomographic angiography, although the secondary costs of incidental findings have not been previously reported. This study investigates the cost of computed tomographic angiography, taking into account the cost of incidental findings found during imaging.
METHODS:Patients undergoing preoperative computed tomographic angiography in preparation for autologous abdominally based breast reconstruction from July of 2010 through May of 2014 were included in this study. Patient medical records were reviewed for imaging findings, need for follow-up, and any additional procedures. Costs were determined using the publicly available Healthcare Bluebook.
RESULTS:A total of 135 patients underwent computed tomographic angiography in preparation for abdominally based microvascular breast reconstruction. Twenty-eight patients (21 percent) were noted to have clinically significant incidental findings recommended for follow-up imaging or procedures. Inclusion of chest imaging with computed tomographic angiography of the abdomen/pelvis to assess for internal mammary and/or thoracodorsal artery patency increased the incidental findings approximately five-fold. The mean cost of computed tomographic angiography increased by 32 percent, from $1267 to $1677 per patient, when incidental findings were included.
CONCLUSIONS:Computed tomography angiography is a tool for the preoperative evaluation of patients desiring autologous breast reconstruction. The true cost of preoperative computed tomographic angiography is likely 30 percent greater than the baseline cost when the subsequent evaluation of incidental findings is included and should be accounted for in future cost-analysis studies.
Radiation-induced morphea (RIM) is a rare but distinctive inflammatory complication of therapeutic radiation.1 It most commonly presents as painful sclerosis of the epidermis and dermis limited to ...the irradiated field. Morphea has also been reported as an immune-related adverse event (irAE) induced by anti-programmed death-1 (PD-1) immune checkpoint inhibitors (ICIs).2,3 We report a patient who first received local radiation therapy to the thorax for lung adenocarcinoma that was complicated by RIM. The patient's morphea then progressed widely beyond the irradiated field in the setting of pembrolizumab therapy. Histopathology and imaging confirmed morphea extending beyond the irradiated field and with deeper muscular and fascial involvement. Pain and edema progressed through multiple lines of toxicity-directed therapy, but ultimately responded significantly to dupilumab. Response was confirmed clinically and radiographically, and the patient was able to resume ICI therapy. This case report highlights the ability of ICIs to induce progression of pre-existing RIM and supports the consideration of dupilumab in refractory cases.
BACKGROUND:Specific International Classification of Diseases, Ninth Revision codes for different methods of autologous breast reconstruction have been introduced recently, prompting investigators to ...use discharge databases to evaluate outcomes of autologous breast reconstruction. The accuracy and validity of these data sources have not been evaluated.
METHODS:All patients who underwent autologous breast reconstruction in a single center from October of 2008 to April of 2013 were retrospectively included. Patient medical records were used as the criterion standard to identify specific autologous procedure performed and any perioperative reoperations. These findings were compared against procedure codes documented in the coded discharge data obtained from hospital billing.
RESULTS:A total of 163 autologous procedures were performed in 115 patients, including 40 pedicled and 37 free transverse rectus abdominis musculocutaneous, 74 deep inferior epigastric perforator, five superficial inferior epigastric artery, four transverse upper gracilis, and three superior gluteal artery perforator flaps. Only 126 of 163 flaps (77 percent) were coded correctly. Twenty-two of 48 bilateral procedures had coding for only one flap. An additional 16 cases were either incorrectly coded as another type of reconstruction or not coded at all. Only 19 of 21 reoperations (90 percent) could be captured by review of the coding alone.
CONCLUSIONS:Using International Classification of Diseases, Ninth Revision, codes alone to evaluate autologous breast reconstructions could result in an incomplete and inaccurate data set, with exclusion of many bilateral flaps. Reoperations during the same hospital stay may also be missed if identified only by a discharge code, thus limiting the evaluation of acute complications.
CLINICAL QUESTION/LEVEL OF EVIDENCE:Diagnostic, II.
The interferon-induced transmembrane (IFITM) proteins have been recently shown to restrict HIV-1 and other viruses. Here, we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, ...specifically antagonize the HIV-1 envelope glycoprotein (Env), thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus-strain dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection and provides insight into the specialized role of IFITMs in HIV infection.
Display omitted
•IFITMs inhibit HIV-1 cell-to-cell infection and impair viral infectivity•IFITMs specifically interact with HIV-1 Env and inhibit Env processing•IFITM incorporation into HIV-1 virions does not correlate with inhibition•IFITM inhibition of primate lentiviruses is virus-strain specific
Yu et al. show that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 Env glycoprotein to inhibit infection. IFITM proteins interact with HIV-1 Env and impair its processing and incorporation into virions. The effects of IFITMs on HIV-1, HIV-2, and SIVs are virus-strain dependent.
PDF
