CD5 + Gamma Delta T-Cell Lymphoproliferative Disorder/Lymphoma Without Cytotoxic Granules in the Skin.

ABSTRACT: We report a case of an unusual and aggressive gamma delta T-cell lymphoproliferative disorder/lymphoma presenting in the skin that lacked the expected cytotoxic markers and had increased expression of CD5, CD20, CD79a, CD30, and PD-1 without CD56. Monoclonal TCR-γ gene rearrangement was identified. A computed tomography scan of the chest, abdomen, and pelvis revealed a 7.7-cm soft-tissue inguinal mass and prominent retroperitoneal and pelvic lymphadenopathy, without hepatosplenomegaly. Flow cytometry finding on peripheral blood was normal. The clinical, morphologic, and immunophenotypic features of this case defy the current World Health Organization and European Organization for Research and Treatment of Cancer classifications, and a similar case has not been reported previously.

Update in Soft-Tissue Filler-Associated Blindness.

BACKGROUND: Soft-tissue filler administration is an increasingly popular minimally invasive cosmetic procedure. Simultaneously, there have been a greater number of adverse events reported, including the devastating complication of blindness. OBJECTIVE: To report cases of filler-related blindness published since 2015. MATERIALS AND METHODS: The Ovid MEDLINE database was searched from January 1, 2015, to August 1, 2018, using a previously described Boolean string. RESULTS: Sixty new cases of filler blindness were identified. The most common type of filler reported was hyaluronic acid (HA) (N = 42, 70.0%), followed by autologous fat (N = 7, 11.7%), and calcium hydroxyapatite (CaHA) (N = 7, 11.7%). The most common injection locations were the nose (N = 33, 55.0%), glabella (N = 21, 35.0%), and forehead (N = 11, 18.3%). Ten cases reported vision restoration (16.7%). Four of the successful cases involved hyaluronidase administration, including 1 retrobulbar hyaluronidase injection. CONCLUSION: Since 2015, there have been 60 newly reported cases of soft-tissue filler blindness. Most recent cases have occurred with HA, which is a shift from previous reports. In HA cases, hyaluronidase injection may be successful in restoring vision if administered promptly. It is imperative for providers to be familiar with strategies for managing soft-tissue filler blindness.

Lower Socioeconomic Status is Associated With Decreased Therapeutic Response to the Biologic Agents in Psoriasis Patients.

BACKGROUND: Lower socioeconomic status is associated with poorer overall health outcomes. However, few studies have examined the impact of socioeconomic status on psoriasis. OBJECTIVE: To examine the impact of individual socioeconomic status on systemic therapeutic outcomes amongst psoriasis patients. METHODS: The study analyzed 156 psoriasis patients treated at the Tufts Medical Center Department of Dermatology from 2008-2014. Individual socioeconomic status was inferred from neighborhood income, defined as the percentage of households with income below the federal poverty line (% below FPL) in the patient's census tract. The following outcomes were compared between socioeconomic groups: improvement in simple measure for assessing psoriasis activity (S-MAPA) score at 12 weeks, primary and secondary drug failure rates, and incidence of documented medication non-adherence. RESULTS: Those patients living in relatively poorer neighborhoods (% below FPL ≤ 10%) experienced a significantly decreased improvement in S-MAPA score at 12 weeks of biologic treatment when compared to those in relatively richer neighborhoods (% below FPL >10%), 23.2% vs. 45.5%, P=0.021. Patients living in poorer neighborhoods also had a significantly higher rate of primary drug failure when treated with biologics (34.7% vs. 18.4%, P=0.039) and were significantly more likely to have ≥ 1 documented instance of medication non-adherence when treated with biologics (45.5% vs. 8.8%, P < 0.001). LIMITATIONS: Retrospective design, small sample size CONCLUSIONS: Our study offers preliminary data that suggests lower socioeconomic status may be associated with decreased clinical response to the biologic agents, presumably through decreased medication adherence.

Biologic and Conventional Systemic Therapies Show Similar Safety and Efficacy in Elderly and Adult Patients With Moderate to Severe Psoriasis.

BACKGROUND/OBJECTIVE: Despite the aging population, few studies have documented the treatment of geriatric psoriasis. The purpose of this study is to compare the efficacy, safety, and prescribing patterns of biologics and conventional systemic medications in elderly versus adult psoriasis. METHODS: All patient visits coded for psoriasis or psoriatic arthritis (ICD-9 696.1 or 696.0) at the Tufts Medical Center General Dermatology Clinic from January 1, 2008, to March 1, 2015 were included in this retrospective cohort study. The outcome measure used was the validated simple-measure for assessing psoriasis activity (S-MAPA), the product of the physician's global assessment and the body surface area. RESULTS: 194 patients who underwent 278 treatment courses were included in the study. 48 patients were included in the elderly cohort (≥ 65 years old) and 146 in the adult cohort (18-64 years old). There was no significant difference in S-MAPA improvement at 12 weeks between the two cohorts when treated with biologics (42.92% improvement in adults, 48.77% in elderly; P=0.498) or conventional systemics (43.96% and 51.82%, respectively; P=0.448). Within the elderly cohort, there was no significant difference in efficacy of biologics versus conventional systemics at any time point. Topical prescription rates were significantly higher in the elderly cohort ( P=0.004) while biologic prescription rates were significantly lower ( P=0.014) despite the same baseline S-MAPA in both age groups. For both biologics and conventional systemics, there was no statistically significant intergroup difference in the rate of adverse events ( P=0.322 for biologics; P=0.581 for conventional systemics) or infection ( P=0.753 for biologics; P=0.828 for conventional systemics). Within the elderly cohort, there was a higher rate of adverse events with conventional systemic treatment than with biologic treatment ( P=0.033). CONCLUSIONS: This study provides preliminary evidence to suggest that biologic and conventional systemic therapies are similarly safe and effective in the elderly and non-elderly cohorts. Within the elderly population, biologics may be a safer option than conventional systemic agents.

Systemic Treatment of Recalcitrant Pediatric Psoriasis: A Case Series and Literature Review.

BACKGROUND/PURPOSE: No systemic drugs are approved by the Food and Drug Administration to treat pediatric psoriasis due to a lack of supporting data. The purpose of this study is to present cases demonstrating the use of systemic drugs in pediatric psoriasis. METHODS: In this case series, data were collected on patients ≤ 18 years old with moderate-to-severe psoriasis treated with systemic medications (traditional systemic drugs or biologics) from 2008 through 2014. Efficacy was measured using the validated simple measure for assessing psoriasis activity (S-MAPA), and the product of the body surface area and Physician Global Assessment. RESULTS: Twenty-seven patients aged 5 to 18 years were eligible, and 56 treatment courses were analyzed. Methotrexate (MTX) was the most frequently prescribed systemic (70%), followed by etanercept (59%). Clearance rates were highest on biologic medications (67% for etanercept and adalimumab, 33% for ustekinumab). Phototherapy, cyclosporine, and MTX were less effective in clearing psoriasis, although they were successful in improving S-MAPA ≥ 50% from baseline 100%, 67%, and 36% of the time, respectively. The most common adverse events were sunburn for patients on narrowband ultraviolet B phototherapy (14%), gastrointestinal intolerance and minor infections for patients on MTX (16% each), and minor infections for patients on etanercept (25%) and adalimumab (33%). The most common reasons for discontinuation were secondary failure (38% for etanercept, 33% for adalimumab) or lack of response (37% for MTX, 33% for cyclosporine). CONCLUSION: Although phototherapy, MTX, and cyclosporine are effective for controlling resistant pediatric psoriasis, concerns about long-term safety or inconvenience have led people to consider biologics in their place. However, there is a lack of literature on the use of biologics in pediatric psoriasis. These cases attest to the safety and efficacy of etanercept, adalimumab, and ustekinumab in pediatric psoriasis, expanding the treatment repertoire and guiding dermatologists in better managing recalcitrant pediatric psoriasis.

Tumor Necrosis Factor Inhibitor Primary Failure Predicts Decreased Ustekinumab Efficacy in Psoriasis Patients.

BACKGROUND: Additional studies are needed to examine the efficacy of ustekinumab in psoriasis patients who have previously been exposed to tumor necrosis factor inhibitors (TNFi). OBJECTIVE: To examine the predictive effect of TNFi primary failure and the number of TNFi exposures on the efficacy of ustekinumab in psoriasis treatment. METHODS: This retrospective study examined 44 psoriasis patients treated at the Tufts Medical Center Department of Dermatology between January 2008 and July 2014. Patients were selected if they were treated with ustekinumab and had ≥ 1 previous TNFi exposure. The following subgroups were compared: patients with vs without a previous TNFi primary failure, and patients with one vs multiple previous TNFi exposures. The efficacy measure used was the previously validated Simple Measure for Assessing Psoriasis Activity (S-MAPA), which is calculated by the product of the body surface area and physician global assessment. The primary outcome was the percentage improvement S-MAPA from course baseline at week 12 of ustekinumab treatment. Secondary outcomes were the psoriasis clearance, primary failure, and secondary failure rates with ustekinumab treatment. RESULTS: Patients with a previous TNFi primary failure had a significantly lower percentage improvement in S-MAPA score at week 12 of ustekinumab treatment compared with patients without TNFi primary failure (36.2% vs 61.1%, P=.027). Multivariate analysis demonstrated that this relationship was independent of patient demographics and medical comorbidities. Patients with multiple TNFi exposures had a non-statistically significant lower percentage S-MAPA improvement at week 12 (40.5% vs 52.9%, P=.294) of ustekinumab treatment compared with patients with a single TNFi exposure. CONCLUSIONS: Among psoriasis patients previously exposed to TNFi, a history of a previous TNFi primary failure predicts a decreased response to ustekinumab independent of patient demographics and medical comorbidities.

Cosmetic complications: rare and serious events following botulinum toxin and soft tissue filler administration.

BACKGROUND: Botulinum toxin (BTX) and soft tissue fillers continue to gain in popularity due to their safety, affordability, quick effects, and short recovery times. With the excellent safety profile of BTX and soft tissue fillers, patients may develop a nonchalant attitude towards treatment with injectables. However, it is important for both patient and physician to be familiar with all the possible complications, both common and uncommon. OBJECTIVE: This article aims to review the rare but serious complications associated with the injectables used in cosmetic dermatology, and the pathogenesis, diagnosis, and management of each. METHODS AND MATERIALS: A literature review for case reports pertaining to rare adverse events following botulinum toxin or soft tissue fillers was performed using the MEDLINE database. RESULTS: Complications of BTX included dry eye syndrome, strabismus and diplopia, superficial temporal artery pseudoaneurysm, neck weakness, hoarseness, and dysphagia. Complications associated with soft tissue fillers included tissue necrosis, inflammatory nodules, hypersensitivity reaction, and blindness and cerebral ischemia. CONCLUSION: The injector should be comfortable in diagnosing and managing the above complications, and the patient should be counseled about these potentially harmful adverse events prior to injection.

An 8-month-old boy with purpuric skin lesions. Acute hemorrhagic edema of infancy.

A previously healthy 8-month-old Hispanic boy presented with a 5-day history of an erythematous, non-pruritic papular eruption on both legs. The eruption was initially diagnosed as impetigo by his primary care practitioner but progressed despite trimethoprim / sulfamethoxazole therapy, with extension to the face, trunk, and all extremities. When the patient subsequently developed a fever of 100.8° F, emesis, diarrhea, and upper respiratory symptoms, he was referred to the pediatric dermatology clinic for evaluation. Further questioning revealed a 3-day febrile illness 6 weeks prior to presentation that was treated with ceftriaxone. Review of systems failed to identify any hematuria, blood in stool, or abdominal pain, but the parents did report swelling of the extremities and face, as well as decreased oral intake. On examination, the infant was in no apparent distress, afebrile, and had mild rhinorrhea. His mucous membranes were unaffected, and no lymphadenopathy or hepatosplenomegaly was noted. Cutaneous exam revealed numerous edematous erythematous to violaceous plaques on the cheeks, arms, buttocks, and legs with minimal involvement of the trunk. Several lesions on the arms had a distinct cockade (rosette or iris-like) pattern. There were no vesicles, bullae, or necrosis. Edema of the bilateral lower extremities was noted. Laboratory work up revealed a normal complete blood count (CBC), comprehensive metabolic panel, creatinine, and urinalysis. Platelets were borderline elevated at 439 TH/µL (140-440 TH/µL), and erythrocyte sedimentation rate and C-reactive protein (CRP) were minimally elevated at 22 mm (0-15 mm) and 3.1 mg/dL (0.0-0.99 mg/dL), respectively.

Frequency of and risk factors for poor cognitive performance in hemodialysis patients.

OBJECTIVE: There are few detailed data on cognition in patients undergoing dialysis. We evaluated the frequency of and risk factors for poor cognitive performance using detailed neurocognitive testing. METHODS: In this cross-sectional cohort study, 314 hemodialysis patients from 6 Boston-area hemodialysis units underwent detailed cognitive assessment. The neuropsychological battery assessed a broad range of functions, with established age-, sex-, and education-matched normative scores. Principal component analysis was used to derive composite scores for memory and executive function domains. Risk factors for each domain were evaluated using linear regression adjusting for age, sex, race, and education status. Analyses were repeated in those with Mini-Mental State Examination (MMSE) score ≥ 24. RESULTS: Compared with population norms, patients on dialysis had significantly poorer executive function but not memory performance, a finding that persisted in the subgroup with MMSE score ≥ 24. In adjusted analyses, vascular risk factors and vascular disease were associated with lower executive function (p < 0.01). CONCLUSIONS: There is a high frequency of poor cognitive performance in hemodialysis patients, primarily affecting executive function. Risk factors for worse executive function include vascular risk factors as well as vascular disease. Normal performance on the MMSE does not preclude impaired cognitive function, because individuals with MMSE score ≥ 24 also have a high frequency of poor cognitive performance.

The kidney disease quality of life cognitive function subscale and cognitive performance in maintenance hemodialysis patients.

BACKGROUND: Cognitive impairment is common but often undiagnosed in patients with end-stage renal disease, in part reflecting limited validated and easily administered tools to assess cognitive function in dialysis patients. Accordingly, we assessed the utility of the Kidney Disease Quality of Life Cognitive Function (KDQOL-CF) scale in comparison to an extensive neuropsychological battery, building on a prior assessment of this potential cognitive screen. STUDY DESIGN: Cross-sectional cohort. SETTING & PARTICIPANTS: Maintenance hemodialysis patients at 6 Boston area dialysis units were administered an extensive neurocognitive battery and the KDQOL-CF at the beginning of a hemodialysis session. PREDICTORS: KDQOL-CF score, depression symptom burden, and demographic and clinical characteristics. OUTCOMES: Neurocognitive performance classified into executive function and memory domains, determined using principal components analysis. MEASUREMENTS: Univariate and multivariable linear regression models adjusting for age, sex, race, and end-stage renal disease cause were used to evaluate the association between KDQOL-CF score and cognitive performance, and test metrics were determined for a KDQOL-CF cutoff score of 60 or less from a maximum score of 100. RESULTS: For 168 prevalent hemodialysis patients, KDQOL-CF score was 76 ± 19 and 40 (24%) had scores of 60 or less, consistent with self-identified worse cognitive performance. There was no significant correlation between KDQOL-CF score and either memory (P = 0.2 and P = 0.3) or executive function (P = 0.1 and P = 0.4) in univariate and multivariable models, respectively. There was a strong correlation between higher KDQOL-CF score and fewer depression symptoms (P < 0.001). Sensitivity of the KDQOL-CF was poor (range, 0.28-0.36), with modest specificity (range, 0.77-0.81) for identifying worse executive function and memory. LIMITATIONS: Cross-sectional study, modest population size, and abbreviated gold-standard cognitive battery. CONCLUSIONS: The KDQOL-CF is a poor determinant of neurocognitive performance in hemodialysis patients, with limited sensitivity. To assess cognitive impairment in hemodialysis patients, better screening tests are essential.

Cardiovascular disease and cognitive function in maintenance hemodialysis patients.

BACKGROUND: Cardiovascular disease (CVD) and cognitive impairment are common in dialysis patients. Given the proposed role of microvascular disease on cognitive function, particularly cognitive domains that incorporate executive functions, we hypothesized that prevalent systemic CVD would be associated with worse cognitive performance in hemodialysis patients. DESIGN: Cross-sectional cohort. SETTING & PARTICIPANTS: 200 maintenance hemodialysis patients without prior stroke from 5 Boston-area hemodialysis units. PREDICTOR: CVD, defined as history of coronary disease or peripheral vascular disease. OUTCOME: Performance on a detailed neurocognitive battery. Primary analyses quantified cognitive performance using principal components analysis to reduce cognitive tests to a processing speed/executive function domain and a memory domain. Multivariable linear regression models adjusted for age, sex, education, race, and other clinical and demographic characteristics. RESULTS: Mean age of participants was 62 ± 18 (standard deviation) years and 75 (38%) had CVD. Individuals with CVD were older and more likely to be men, have diabetes, and be current or former smokers. In adjusted models, individuals with CVD performed 0.50 standard deviation worse (P < 0.001) on tests assessing processing speed/executive function, whereas there was no difference in performance on tests of memory. Similar results were seen assessing individual tests, with performance on the Block Design, Digit Symbol Coding, and Trail Making Tests A and B significantly associated with CVD in age-, sex-, education-, and race-adjusted analyses and approaching significance in fully adjusted models. LIMITATIONS: CVD ascertainment dependent on patient recall and dialysis unit documentation. No brain imaging. CONCLUSIONS: The presence of CVD is associated with worse cognitive performance on tests of processing speed and executive functioning in hemodialysis patients and identifies a high-risk population for greater difficulty with complex tasks.

Cognitive function and dialysis adequacy: no clear relationship.

BACKGROUND/AIMS: Cognitive impairment is common in hemodialysis patients and may be impacted by multiple patient and treatment characteristics. The impact of dialysis dose on cognitive function remains uncertain, particularly in the current era of increased dialysis dose and flux. METHODS: We explored the cross-sectional relationship between dialysis adequacy and cognitive function in a cohort of maintenance hemodialysis patients. Adequacy was defined as the average of the 3 most proximate single pool Kt/V assessments. A detailed neurocognitive battery was administered during the 1st hour of dialysis. Multivariable linear regression models were adjusted for age, sex, education, race and other clinical and demographic characteristics. RESULTS: Among 273 patients who underwent cognitive testing, the mean (SD) age was 63 (17) years and the median dialysis duration was 13 months, 47% were woman, 22% were African American, and 48% had diabetes. The mean (SD) Kt/V was 1.51 (0.24). In univariate, parsimonious and multivariable models, there were no significant relationships between decreased cognitive function and lower Kt/V. CONCLUSION: In contrast to several older studies, there is no association between lower Kt/V and worse cognitive performance in the current era of increased dialysis dose. Future studies should address the longitudinal relationship between adequacy of dialysis and cognitive function to confirm these findings.