Cutaneous adverse events in 155 patients with metastatic melanoma consecutively treated with anti-CTLA4 and anti-PD1 combination immunotherapy: Incidence, management, and clinical benefit.

BACKGROUND: In response to the increased use of combination checkpoint inhibitors (CPIs) and the resulting increased cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated with combination CPIs to characterize CAE features and their clinical impact, correlation to adverse events in other organs, and correlation to tumor response. METHODS: Patients from the authors' institutional database who received at least 1 dose of ipilimumab in combination with either nivolumab or pembrolizumab between January 1, 2012, and December 31, 2017, for stage IV or unresectable stage III melanoma were identified. The time to next treatment (TTNT) was calculated from the start of CPI therapy to the start of the next treatment or death, and the development of CAEs was tested in a time-dependent Cox regression to identify associations with TTNT. RESULTS: Eighty-one patients (52.3%) experienced a total of 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), and pruritus without rash (8.7%). The median times to the onset and resolution of CAEs were 21 days (range, 0-341 days) and 50 days (range, 1-352 days), respectively. Most CAEs resolved after patients entered the CPI maintenance phase and treatment with oral antihistamines with or without topical steroids. CPI discontinuation occurred in 4 patients (2.6%) because of CAEs, in 49 (31.6%) because of other immune-related adverse events, and in 20 (12.9%) because of melanoma progression or death. For patients definitively treated with CPIs (n = 134; 86.5%), TTNT was significantly longer with CAEs than without CAEs (hazard ratio, 0.567; 95% CI, 0.331-0.972; P = .039). CONCLUSIONS: CAEs were mostly reversible and rarely required therapy discontinuation. The development of CAEs was associated with a longer TTNT, and this suggested a possible clinical benefit.

Linezolid as a treatment option for cutaneous non-tuberculous mycobacterial infections.

Cutaneous non-tuberculous mycobacterial (NTM) infections have rapidly increased in incidence in recent years. Currently there is no standard treatment and the variable and nonspecific ways in which cutaneous NTM infection presents makes it a therapeutic and diagnostic challenge. We describe a 67-year-old immunocompetent woman with cutaneous NTM infection after she recently underwent a root canal procedure. Although the species was not identified and she was unable to tolerate multiple antibiotics, she ultimately responded well to three months of treatment with linezolid. Given that cutaneous NTM infection can present in immunocompetent patients and that the incidence is rising, it is important for clinicians to maintain a high index of clinical suspicion, especially in patients with a recent history of surgery, trauma, or cosmetic procedures. Linezolid has coverage against non-tuberculous mycobacteria and is an effective therapeutic option for cutaneous NTM cases in which identification to the species level is not possible or when adverse effects limit therapeutic options.

Exploring 5-minute heart rate variability in spinal cord injury during acute inpatient rehabilitation.

To explore the use of 5-minute heart rate variability (HRV) during inpatient rehabilitation in the acute phase of traumatic spinal cord injury (SCI).Longitudinal observational study.Acute inpatient rehabilitation (AIR).10 patients with acute traumatic SCI.5-minute HRV supine recordings twice daily on three different days per patient.HRV values were evaluated (1) within a single day (Early versus Late); (2) across the inpatient admission (initial, mid, and discharge); (3) by SCI phenotypes and by clinical outcomes (ex. pressure injuries (PI)).Patients had an average age of 38 years, 80% male, and 40% with tetraplegia. There were no HRV differences between Early and Late recordings, across the inpatient admission, demographics, or SCI phenotype. However, improvement in neurologic exam was accompanied by increased parasympathetic tone (mean RR increased by 172 ms SD 61, P = .005). Patients with PI demonstrated lower sympathetic (SNS) activity (decreased LF by 472 ms2 SD 240, P = .049) and lower PNS activity (decreased RMSSD by 1.2 ms SD 0.5, P = .02), compared to no PI. Comparisons to uninjured reference values and chronic SCI suggest a changing autonomic nervous system (ANS) from uninjured to acute to chronic as measured by HRV. CONCLUSIONS: This preliminary evidence suggests HRV in acute SCI is stable across time and day during inpatient rehabilitation and may be correlated to clinical sequalae of ANS dysfunction and neurologic recovery. Comparisons to published work suggest that HRV may measure the progression in the ANS from acute to chronic phase after SCI.

Annular lichenoid diseases.

Annular lichenoid diseases encompass a diverse range of pathologies that present as circular, raised, or flat lesions that may vary in size and number. Examples include annular lichenoid dermatitis of youth, annular lichen planus, erythema dyschromicum perstans, erythema multiforme, fixed drug eruption, lichen sclerosus, neonatal lupus, porokeratosis, subacute cutaneous lupus erythematosus, and lichenoid syphilis. Clinical morphology and histopathology can differentiate these entities.