Sex and gender differences in adverse events following influenza and COVID-19 vaccination.

INTRODUCTION: Active and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. In a predominately young adult female population of healthcare workers, we sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized. METHODS: This cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the mandatory annual fall 2019-2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns. Vaccine recipients were enrolled the day of vaccination and AE surveys were administered two days post-vaccination for bivalent COVID-19 and influenza vaccine recipients. Data were collected regarding the presence of a series of solicited local and systemic AEs. Open-ended answers about participants' experiences with AEs also were collected for the COVID-19 vaccine recipients. RESULTS: Females were more likely to report local AEs after either influenza (OR = 2.28, p = 0.001) or COVID-19 (OR = 2.57, p = 0.008) vaccination compared to males, regardless of age or race. Males and females had comparable probabilities of reporting systemic AEs after either influenza (OR = 1.18, p = 0.552) or COVID-19 (OR = 0.96, p = 0.907) vaccination. Hormonal birth control use did not impact the rates of reported AEs following influenza vaccination among reproductive-aged female HCWs. Women reported more interruptions in their daily routine following COVID-19 vaccination than men and were more likely to seek out self-treatment. More women than men scheduled their COVID-19 vaccination before their days off in anticipation of AEs. CONCLUSIONS: Our findings highlight the need for sex- and gender-inclusive policies to inform more effective mandatory occupational health vaccination strategies. Further research is needed to evaluate the potential disruption of AEs on occupational responsibilities following mandated vaccination for healthcare workers, a predominately female population, and to more fully characterize the post-vaccination behavioral differences between men and women.

Research that addresses both the sex and gender differences of vaccine outcomes and behaviors is lacking. In this survey study of healthcare workers, comprised of mostly reproductive-aged females/women, we investigated biological sex (male/female) and gender (man/woman) differences in vaccine adverse events and outcomes following either influenza or bivalent COVID-19 vaccination.Regardless of age or race, females were more likely to report local (at injection site), but not systemic (whole body), adverse events than males, consistent across influenza and bivalent COVID-19 vaccine cohorts. Sex hormones are hypothesized to play a role in the differences in immune response following vaccination between males and females. We investigated if hormonal birth control use among females may be associated with differences in vaccine adverse events among the influenza vaccine cohort. However, there was no difference in the likelihood of reporting adverse events between birth control users and non-users. Based on open-ended responses to survey questions, women were found to report more interruptions to their daily routine than men following COVID-19 vaccination. Women were also more likely to seek out self-treatment with over-the-counter medication and intentionally schedule their vaccination around days off in anticipation of adverse events.With nearly 80% of healthcare jobs held by women, even higher for direct patient care positions like nursing, females/women may be disproportionately impacted by mandated annual vaccinations. Vaccinations are necessary for the prevention of disease transmission; however, our findings highlight a need for more equitable occupational vaccine strategies that consider both sex and gender differences.

Sex and gender differences in adverse events following receipt of influenza and COVID-19 vaccination among healthcare workers.

Introduction: Active and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. We sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized. Methods: This cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the annual fall 2019-2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns. Vaccine recipients were enrolled the day of vaccination and AE surveys were administered two days post-vaccination (DPV) for bivalent COVID-19 and Influenza vaccine recipients. Data were collected regarding the presence of a series of solicited local and systemic AEs. Open-ended answers about participants' experiences with AEs also were collected for the COVID-19 vaccine recipients. Results: Females were more likely to report local AEs after influenza (OR=2.28, p=0.001) or COVID-19 (OR=2.57, p=0.008) vaccination compared to males, regardless of age or race. Males and females had comparable probabilities of reporting systemic AEs after influenza (OR=1.18, p=0.552) or COVID-19 (OR=0.96, p=0.907) vaccination. Exogenous hormones from birth control use did not impact the rates of reported AEs following COVID-19 vaccination among reproductive-aged female HCWs. Women reported more interruptions in their daily routine following COVID-19 vaccination than men and were more likely to seek out self-treatment. More women than men scheduled their COVID-19 vaccination before their days off in anticipation of AEs. Conclusions: Our findings highlight the need for sex- and gender-inclusive policies to inform more effective occupational health vaccination strategies. Further research is needed to evaluate the potential disruption of AEs on occupational responsibilities following mandated vaccination for healthcare workers and to more fully characterize the post-vaccination behavioral differences between men and women. KEY MESSAGE: What is already known on this topic: ⇒ Among diversely aged adults 18-64 years, females report more AEs to vaccines, including the influenza and COVID-19 vaccines, than males.⇒ Vaccine AEs play a role in shaping vaccine hesitancy and uptake.⇒ Vaccine uptake related to influenza and COVID-19 are higher among men than women.⇒ Research that addresses both the sex and gender disparities of vaccine outcomes and behaviors is lacking.What this study adds: ⇒ This prospective active reporting study uses both quantitative and qualitative survey data to examine sex and gender differences in AEs following influenza or COVID-19 vaccination among a cohort of reproductive-aged healthcare workers.How this study might affect research, practice, or policy: ⇒ Sex and gender differences in AEs and perceptions relating to vaccination should drive the development of more equitable and effective vaccine strategies and policies in occupational health settings.

Association between childhood negative life events with alcohol expectancies in early adolescence: Cumulative risk and latent class approaches.

BACKGROUND: The present study aims to investigate the effects of childhood negative life events (NLEs) on alcohol expectancies (AEs) in early adolescence through cumulative risk and latent class approaches. METHODS: Data were obtained from a prospective cohort of 945 sixth graders (age 11-12) ascertained from 17 elementary schools in northern Taiwan (response rate = 61.0 %wt); subsequent assessments were conducted during eighth grade (n = 775, follow-up rate [FR] = 82.6 %wt). Information concerning socio-demographics, 14 NLEs, alcohol-related experience, and four-domain AEs was collected by self-administered questionnaires at childhood and follow-up. Latent class and multivariate analyses were used to evaluate the association estimates. RESULTS: Nearly one half of children had experienced at least one NLE in sixth grade, with one-tenth experiencing four or more NLEs. Three latent classes of NLEs were identified: "lesser experience (68.1 %wt)," "stressed relationship (27.6 %wt)," and "family instability (4.3 %wt)." The observed NLE-associated increase in AEs was relatively stronger in the cumulative approach: children experiencing four or more NLEs (ßwt = 1.27, 95 % CI = 0.27-2.27) and in the "stressed relationship" NLE class appeared to develop greater AEs (ßwt = 0.86, 95 % CI = 0.30-1.42). Moreover, such NLE-associated increase was especially salient in the AE domains regarding "global positive transformation" and "promoting relaxation or tension reduction". CONCLUSIONS: Our results provide insight into which experiences of multiple and "stressed relationship" negative life events arising from the family context in childhood may shape endorsed alcohol expectancies in adolescence, and implied that such effects may not uniformly operate across AE domain.

Atypical carcinoid metastasis to the skin.

Carcinoid tumors are derived from neuroendocrine cells, and are most frequently found in the gastrointestinal tract and bronchopulmonary system. Cutaneous involvement of carcinoid tumors is relatively rare, with isolated case reports in the literature. We detail a patient with stage IV pulmonary atypical carcinoid tumor with skin metastasis. This case is unusual because the patient did not have any erythema or induration of the scalp, only a complaint of pain. On biopsy, the tumor cells had cytologic features of a carcinoid tumor, but were arranged as infiltrating cords, small aggregates and single units, rather than the organoid or trabecular pattern seen in the primary tumor. Further, along with neuroendocrine markers, the tumor cells had the staining pattern of cytokeratin 7+/cytokeratin 20-/thyroid transcription factor-1+, supporting a carcinoid tumor of lung origin. Thus, this case of skin metastasis from an atypical pulmonary carcinoid tumor illustrates a unique clinical and histologic presentation.

Facial follicular porokeratosis: a case report.

Porokeratosis is a disorder of keratinization, characterized clinically by a peripheral keratotic ridge and histologically by the cornoid lamella. We describe a patient with follicular porokeratosis with a distinctive clinical presentation. We believe that follicular porokeratosis is a unique histopathologic variant of porokeratosis, with cornoid lamellae centered in follicular infundibula. Further, this is the only report of follicular porokeratosis involving the face exclusively.

Massive localized lymphedema: A soft tissue process that may present to dermatologists.

Massive localized lymphedema (MLL) is a clinically and histologically distinct entity seen in morbidly obese patients. We describe two obese patients with MLL in the lower abdomen and suprapubic area. Biopsies showed characteristic histologic features of an expanded dermis with lymphangiectases, fibrotic septae and focal fat necrosis. One patient had long-standing hypothyroidism, an association previously reported. This disease is frequently complicated by recurrent cellulitis and may be amenable to surgery. Patients with MLL may present to dermatologists, and this disease has characteristic histopathologic findings that may mimic liposarcoma to the unaware dermatopathologist.

Childhood social context in relation to alcohol expectancy through early adolescence: A latent profile approach.

BACKGROUND: The present study aims to (i) identify patterns in the changes of endorsed positive alcohol expectancies (AEs) through early adolescence and (ii) examine associated childhood social context predictors of such profiles. METHODS: We used three waves of longitudinal data from the Alcohol-Related Experiences among Children. The baseline sample comprised 928 6th graders from 17 elementary schools in northern Taiwan (response rate = 60 %); subsequent follow-up was conducted at 7th and 8th grade (follow-up rate = 88 %). Data concerning three domains of positive AEs (i.e., global positive transformation, enhancing social behaviors, and promoting relaxation), social context, and alcohol drinking were collected by self-administered questionnaires. Longitudinal latent profile and survey multinomial logistic regression analyses were used to evaluate the association estimates, stratified by childhood alcohol initiation. RESULTS: Three distinct profiles (decreasing, stable, and increasing) of positive AEs were identified for the alcohol-naïve children (n = 466); observing paternal drinking and watching TV more than two hours per day at baseline were strongly linked with the stable and increasing AE profiles (aOR = 1.96-4.80). For the alcohol-experienced children, four profiles (low decreasing, low increasing, high decreasing, and high increasing) emerged; observing maternal drinking was predictive for the high-increasing profile (aOR = 2.94). Regardless of childhood alcohol initiation, recent alcohol use appeared to be the strongest predictor for the increasing profiles of positive AEs. CONCLUSIONS: Strategies addressing pro-alcohol social contexts that facilitate a prominent increase in positive AEs should be considered when devising preventive programs targeting underage drinking behaviors and problems.

Porokeratotic eccrine ostial and dermal duct nevus: a report of 2 cases and review of the literature.

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare disorder of keratinization involving the intraepidermal eccrine duct (acrosyringium). We detail two examples of this unique clinicopathological entity--one with a more typical clinical presentation and one with a solitary lesion and late adult onset. In addition, we discuss the distinctive histologic and immunohistochemical findings and review the literature.

Histopathology and X-ray microanalysis of foreign material on facial keratoses.

Opaque exogenous material was frequently observed on the surface of keratoses during routine sign out by one of us (H.K.). To investigate this material further, 300 consecutive seborrheic keratoses were reviewed: 100 cases from the face of women, 100 cases from the face of men, and 100 cases from the trunk of men and women. All cases were evaluated by light microscopy for the presence and quantity of exogenous material, and 14 cases were studied by x-ray microanalysis to assess its composition. The material was present on 54% of facial keratoses from predominantly older women (mean age 67 years), 5% of facial keratoses from men, and 9% of truncal keratoses from men and women. The x-ray microanalysis showed the presence of a variety of elements, including titanium (13 cases), silicon (12 cases), iron (9 cases), aluminum (8 cases), magnesium (8 cases), zinc (4 cases), barium (2 cases), and bismuth (2 cases). We believe that the exogenous material represents cosmetic products such as colored facial cosmetics, sunscreens, and moisturizers. Further, because the exogenous material was found predominantly on facial keratoses of older women, the presence of this material in a specimen may serve as a clue to the patient's gender, age, and biopsy site.

Linear psoriasis.

A 33-year-old man presented with verrucous, red-brown papules, which coalesced into linear plaques on the right buttock, waist, thigh, and genitals. A skin biopsy was consistent with psoriasis, and the unilateral distribution in a linear pattern led to a diagnosis of linear psoriasis, which is a rare variant of psoriasis. Although histopathologically it can be difficult to distinguish from inflammatory linear verrucous epidermal nevus (ILVEN), linear psoriasis presents in adulthood and responds to conventional topical antipsoriatic therapies.

Rowell syndrome (systemic lupus erythematosus + erythema multiforme).

A 61-year-old woman with a history of chilblains and systemic lupus erythematosus (SLE) for 15 years presented with annular, erythematous, scaly papules and plaques on her face, neck, chest, abdomen, back, arms, and legs. A biopsy specimen showed a destructive interface dermatitis with extensive epithelial cell necrosis, which was consistent with lupus erythematosus with combined subacute cutaneous lupus and erythema multiforme-like features. These findings are most compatible with a diagnosis of Rowell syndrome. Rowell syndrome and its relation to lupus erythematosus and erythema multiforme are discussed.

Eosinophilic fasciitis/generalized morphea overlap.

A 50-year-old woman presented with a three-month history of violaceous, non-tender, indurated plaques on the chest, abdomen, breasts, and proximal portions of the arms and legs. An incisional biopsy specimen showed changes consistent with a diagnosis of inflammatory morphea. Over the course of one year, the patient began to develop signs and symptoms suggestive of a diagnosis of eosinophilic fasciitis, which included the characteristic groove sign on the upper extremities. Although our patient did not exhibit peripheral or histopathologic evidence of eosinophilia, the diagnosis of eosinophilic fasciitis could still be made because the aforementioned phenomena are not required for diagnosis. Multitude treatment regimes have been reported in the literature as single case reports or small patient series. Our patient was maintained on methrotrexate, oral glucocorticoids, and etanercept with improvement of skin lesions and mobility.

Systemic drug-related intertriginous and flexural exanthema (SDRIFE).

A 72-year-old man with a history of metastatic melanoma presented with a two-day history of erythematous and edematous plaques, with scattered bullae on the neck, chest, axillae, and inguinal and gluteal folds, which began five days after infusion of an experimental drug. The clinical and histopathologic findings were consistent with systemic drug-related intertriginous and flexural exanthema (SDRIFE), which is an uncommon drug reaction that results in symmetric erythema that affects the buttocks, groin, and/or thighs as well other flexural folds. The clinical manifestations of SDRIFE are highly characteristic and include distinctive primary cutaneous lesions with a specific distribution and course; however, heterogeneity exists with respect to histopathologic features, skin test results, and in vitro investigations. The exact mechanism of SDRIFE remains unknown but is thought to result from a type IV delayed hypersensitivity immune response. Treatment is symptomatic and includes topical or oral glucocorticoids.

Fixed cutaneous sporotrichosis.

Sporotrichosis is a subcutaneous mycosis that is caused by Sporothrix schenckii. Whereas the most common clinical presentation is the lymphocutaneous form, the fixed cutaneous form is not uncommon. Important clues from the clinical history, such as travel and occupation, can help to raise the suspicion of this infection in the differential diagnosis. However, histopathologic and tissue culture, which often require multiple specimens, are necessary to confirm the diagnosis. We present a patient with fixed cutaneous sporotrichosis whose delayed diagnosis led to appreciable scars and morbidity.

Generalized eruptive keratoacanthomas of Grzybowski.

A 48-year-old man presented with a two-year history of a generalized, pruritic eruption that was associated with numerous, dome-shaped papules and nodulocystic lesions. Biopsy specimens have shown keratoacanthomas and a lichenoid dermatitis. Evaluation for malignant conditions has been negative. Owing to the constellation of findings, a diagnosis of generalized eruptive keratoacanthomas of Grzybowski associated with lichenoid dermatitis and acneiform lesions is favored. The patient is currently on a trial of acitretin.

Leisure activity participation in relation to alcohol purchasing and consumption in adolescence.

BACKGROUND: Building upon the socioecological perspective, this study examines prospective associations linking leisure activity participation with alcohol purchasing and consumption in early adolescence. METHODS: A total of 1763 seventh graders (age 12-13 years) were recruited from middle schools in urban Taiwan via multi-stage sampling and followed-up 1.5 years later during ninth grade. Information about leisure activities, covariates (i.e., gender, puberty development, family structure, parental educational attainment, monthly allowance, peer drinking, and childhood alcohol experience), and two outcome variables (i.e., alcohol purchasing and drinking behaviors) was gathered via web-based self-administered questionnaires. Data concerning alcohol outlets and recreational resource for each community district were retrieved from official statistics and commercial sources. Two-level hierarchical generalized linear models were used to evaluate association estimates. FINDINGS: Five percent of ninth graders ever purchased alcohol and nearly one in seven drank alcohol on three or more occasions (i.e., occasional drinking) in the past year. Sports, unstructured, and organized leisure activities were not linked with illegal alcohol purchasing when community contexts were statistically adjusted; a higher community on-premised alcohol outlet density increased alcohol purchasing by 94% (95% CI = 1.24-3.06). In contrast, unstructured leisure activity participation at 7th grade predicted occasional drinking (adjusted Odds Ratio [aOR] = 5.52; 95% CI = 3.13-9.74). Sports participation was associated with reduced risk of occasional drinking in the communities with high unregulated alcohol outlets (aOR for interaction = 0.58; P < .001). CONCLUSION: Our research provides insights to differential roles of leisure activity participation in shaping adolescents' commercial alcohol access and occasional drinking. Macro-social contexts should be considered in the efforts to reduce underage drinking problems through leisure activities.

Doxorubicin-induced hyperpigmentation.

A 39-year-old man with human immunodeficiency virus infection and Kaposi sarcoma on HAART therapy and doxorubicin presented in 2007 with a hyperpigmented tongue. Physical examination also showed hyperpigmented patches on the mucosal aspects of the lips and longitudinal dark bands on multiple nails. A skin biopsy specimen showed pigmentary alteration. Such hyperpigmentation has been described in numerous case reports and case series and has been reported to resolve within weeks to months of cessation of doxorubicin.

Perforating collagenosis.

A 55-year-old man presented with a three-week history of pruritic, erythematous papules with hyperkeratotic dells on the dorsum of the left hand, which was preceded by swelling, redness and itching. Histopathologic examination showed an acanthotic epidermis with a central invagination filled with a plug composed of parakeratotic debris, collagen, and inflammatory cells. These findings are consistent with acquired reactive perforating collagenosis, which is most frequently reported in patients with pruritus and underlying diabetes mellitus or chronic renal insufficiency. Topical and oral retinoids and topical and intralesional glucocorticoids have been reported to be effective in some patients in case series.

Linear lichen planus.

A 50-year-old man presented with pruritic, hyperpigmented papules and plaques on the right lower extremity following Blaschko lines. A skin biopsy specimen was consistent with lichen planus (LP). Linear LP accounts for less than 0.2 percent of all patients with LP, and the segmental formation is thought to be due to a postzygotic mutation that affects one of the genes predisposing its development. This loss of heterozygosity may occur from a mutation, deletion, or DNA recombination and leads to the formation of a keratinocyte clone that is more susceptible to development of the skin disease. Histopathologically, linear LP is identical to LP, with the presence of hyperkeratosis, focal hypergranulosis, irregular acanthosis with a sawtooth appearance, vacuolar change of the basal-cell layer, and a dense band-like lymphocytic infiltrate at the dermal-epidermal junction. It is important to differentiate linear LP from lichen striatus, inflammatory linear verrucous epidermal nevus, linear psoriasis, and linear Darier-White disease, which have different presentations clinically and histopathologically.

Extramammary Paget disease.

A 59-year-old man presented with a well-demarcated, tender ulcer at the base of the penile shaft that had been present for approximately five years. The ulcer had been responsive neither to topical antibacterials, antifungals, and glucocorticoids nor to oral acyclovir. A biopsy specimen showed an intra-epidermal neoplasm consistent with extramammary Paget disease (EMPD) based on light microscopy and immunohistochemistry. Patients with EMPD require extensive medical evaluation because of its association with adnexal carcinoma and visceral malignant conditions. Evaluation should include a full body skin and lymph node examination, colonscopy, cystoscopy, and sex-specific studies including pelvic and breast examinations, with imaging for women and prostate examination with prostate specific antigen levels for men. Close monitoring after treatment is important because of the recognized risk of recurrence and malignant conditions.