Chemical exposures and demographic associations in cutaneous T-cell lymphoma: a large single institution physician validated cohort study.

Cutaneous T-cell lymphomas (CTCL) are a rare group of T-cell neoplasms which infiltrate the skin and can result in substantial morbidity and mortality. Risk factors for CTCL are still poorly understood though recent studies suggest chemical exposures may play a role in its development. To further characterize patient-centered risk factors for CTCL, especially compared with matched controls, we performed one of the largest prospective cohort survey studies to date to examine patient-reported exposures and health-related quality of life (HRQoL) in association with concurrent clinical disease characteristics. Patient demographics, lifestyle factors, and chemical exposures were collected via clinical data and surveys. Descriptive statistics, ANOVA, Chi-square tests and t tests were utilized to compare patient-reported exposures and HRQoL in patients with CTCL versus matched healthy controls (HC). Statistically significant differences were identified between patients and HC in terms of race (non-white race 22.4% in CTCL patients vs. 18.8% in HC, P = 0.01), and education level (high school or less 41.6% in CTCL patients vs. 14.3% in HC, P = 0.001), but not with Fitzpatrick skin type (P = 0.11) or smoking status (P = 0.28). Notably, 36.0% of the CTCL patients reported exposures to chemicals, a near threefold increased percentage when compared to HC (12.9%). Among various chemical exposures, 27.0% of the CTCL patients specifically reported industrial chemical exposure, a more than two-fold increased percentage when compared to HC (12.9%). Itch and pain were significantly associated with skin disease severity (as evaluated by CTCL-specific mSWAT score) in advanced stage disease (stages IIB-IVB) (r = 0.48 and 0.57, P < 0.05). Itch and body mass index (BMI) were weakly associated with skin disease severity in early-stage disease (stages IA-IIA) (r = 0.27 and 0.20, P < 0.05).

Role of Antigenic Stimulation in Cutaneous T-Cell Lymphomas.

Cutaneous T-cell lymphoma (CTCL) involves a clonal expansion of malignant cells accumulating in the skin, a primary barrier site. CTCL has long been hypothesized to be caused or perpetuated by chronic antigen stimulation due to unknown exposures. These antigenic triggers, defined as any element that may cause activation of malignant T cells through TCR signaling, have been hypothesized to range from chemicals to microbes. This review covers current evidence supporting chemical and microbial stimuli that may act as antigenic triggers of CTCL and summarizes novel areas of investigation, in which the potential antigenicity of the exposure is still unknown.

Epstein-Barr Virus-Associated Lymphomatoid Papules: A Sign of Immunosuppression Resembling Lymphomatoid Papulosis.

ABSTRACT: Epstein-Barr virus (EBV)-positive lymphoproliferative disorders associated with immunodeficiency constitute a spectrum of lymphoid and plasma cell proliferations that vary in cytomorphology, immunophenotype, and clinical behavior. CD30-positive cutaneous lymphocytic infiltrates with EBV expression and lymphomatoid papulosis-like presentations have been rarely reported. This retrospective study assessed the clinical and histopathological characteristics of EBV-positive cases with papulonodular morphologies and CD30 positivity seen by Northwestern Medicine Dermatopathology. Twelve patients (7M:5F, mean age 69 years) were presented with papular cutaneous lesions without antecedent patch/plaque disease. Nine cases were associated with known immunosuppression in the setting of transplant-related therapies (n = 4), hematopoietic malignancy (n = 2), post-transplant hematopoietic malignancy (n = 1), and autoimmune disease treatment (n = 2). Two patients had age-related immunosenescence. Four patients demonstrated EBV viremia; for 2 patients, this finding comprised the first sign of immunosuppression. Workup was negative for systemic lymphoma in all patients. Various treatment strategies were used, including observation (n = 3), discontinuation/reduction of immunosuppression (n = 3), rituximab (n = 4), and steroids (n = 4). At mean 30-month follow-up, 4 patients (33.3%) were alive, 3 with and 1 without disease. Eight patients (67.6%) had died, 3 after lesional resolution and 5 with recurrent disease. Biopsies revealed mixed lymphoid infiltrates composed of atypical CD30-positive T cells (n = 5) or B cells (n = 7) with variable EBV-encoded small RNA expression. These cases suggest clinicopathologic presentations resembling lymphomatoid papulosis with atypical, large CD30-positive, EBV-positive cells could comprise first sign of potentially serious immunodeficiency and should prompt evaluation for EBV viremia. These cases also broaden the current picture of immunodeficiency-associated lymphoproliferative disorders to include lymphomatoid papulosis-like clinical presentations.

Perceptions of telehealth among inpatient consultative dermatology providers and practice patterns during COVID-19.

Use of inpatient teledermatology increased during the COVID-19 pandemic. We surveyed the Society for Dermatology Hospitalists to better characterize the impact of COVID-19 on teledermatology use by inpatient dermatology providers, particularly on provider perceptions of teledermatology. Prior to the COVID-19 pandemic, 40% (8/20) of surveyed providers had used telehealth at their institution to help perform inpatient consults, while 90% (18/20) adapted use of teledermatology during the pandemic. 80% (16/20) reported that their opinion of teledermatology changed as a result of the COVID-19 pandemic, with the vast majority (87.5%, 14/16) reporting having a more positive opinion. Benefits of teledermatology included efficiency, ability to increase access safely, and ability for clinicians to focus on complex cases. Some providers expressed concerns over the potential implications regarding the perception of dermatology within medicine, limitations of inadequate photos, and breakdowns in communication with consulting teams and patients. Robust algorithms and or utilization criteria of teledermatology may help to mitigate risk, while increasing access to inpatient dermatologic evaluation.

Monkeypox outbreak, vaccination, and treatment implications for the dermatologic patient: Review and interim guidance from the Medical Dermatology Society.

Rapid human-to-human transmission of monkeypox has created a public health emergency requiring prompt, multidisciplinary attention. Dermatologists are at the forefront of diagnosis due to the disease-defining skin lesions. Moreover, patients with pre-existing skin disease and those who are on immunosuppressive medications for skin disease may be at increased risk of severe infection. In this review, a panel of authors with expertise in complex medical dermatology and managing patients on immunosuppression reviews the literature and provides initial guidance for diagnosis and management in dermatology practices. Though there are knowledge gaps due to a lack of controlled studies, we support use of replication-deficit vaccines in all dermatologic patients who meet qualifying risk or exposure criteria. We offer strategies to optimize vaccine efficacy in patients with immunosuppression. We discuss alternative post-exposure treatments and their safety profiles. Finally, we outline supportive care recommendations for cutaneous manifestations of monkeypox. Large scale epidemiologic investigations and clinical trials will ultimately revise and extend our guidance.

High-Dose Vitamin D for the Management of Toxic Erythema of Chemotherapy in Hospitalized Patients.

This case series describes the outcome of high-dose vitamin D treatment in 6 inpatients with acute skin injury.

Retrospective analysis of sepsis in cutaneous T-cell lymphoma reveals significantly greater risk in Black patients.

BACKGROUND: Sepsis is a leading cause of morbidity, mortality, and resource utilization among patients with cutaneous T-cell lymphoma (CTCL). OBJECTIVE: To characterize the demographic, clinical, and microbial attributes distinguishing patients with CTCL sepsis from other patients with non-Hodgkin lymphoma (NHL) sepsis and patients with CTCL in general. METHODS: Two-part retrospective cohort study at an academic medical center from 2001-2019 involving patients with CTCL (n = 97) and non-CTCL NHL (n = 88) admitted with sepsis, and a same-institution CTCL patient database (n = 1094). Overall survival was estimated by Kaplan-Meier analyses. RESULTS: Patients with CTCL sepsis were more likely to be older, Black, experience more sepsis episodes, die or be readmitted within 30 days of an inpatient sepsis episode, and develop Gram-positive bacteremia than patients with non-CTCL NHL sepsis. Staphylococcus aureus and Escherichia coli were the most frequently speciated organisms in CTCL (26%) and non-CTCL NHL (14%), respectively. No between-group differences were identified regarding sex, presence of central line, chemotherapy use, or disease stage. Compared with general patients with CTCL, patients with sepsis were Black and exhibited advanced-stage disease, higher body surface area involvement, and higher lactate dehydrogenase levels. LIMITATIONS: Single institution, retrospective nature may limit generalizability. CONCLUSION: Awareness of CTCL-specific risk factors is crucial for guiding sepsis prevention and improving patient outcomes.

Gut microbiota analyses of cutaneous T-cell lymphoma patients undergoing narrowband ultraviolet B therapy reveal alterations associated with disease treatment.

Recent studies have shown a close relationship between cutaneous T-cell lymphoma (CTCL) and its microbiome. CTCL disease progression is associated with gut dysbiosis and alterations in bacterial taxa parallel those observed in immunologically similar atopic dermatitis. Moreover, the microbial profile of lesional skin may predict response to narrowband ultraviolet B (nbUVB), a common skin-directed therapy. However, the relationship between the gut microbiome, an immunologically vital niche, and nbUVB remains unexplored in CTCL. Herein, we performed 16S rRNA sequencing and PICRUSt2 predictive metagenomics on DNA extracted from stool swabs of 13 CTCL patients treated with nbUVB, 8 non-treated patients, and 13 healthy controls. Disease response was assessed with modified Severity Weighted Assessment Tool (mSWAT); of nbUVB-treated patients, 6 improved (decreased mSWAT), 2 remained stable, and 5 worsened (increased mSWAT). Protective commensal bacteria including Lactobacillaceae and Erysipelatoclostridiaceae were significantly less abundant in CTCL patients compared to controls. With treatment, the CTCL gut microbiome exhibited decreased phylogenetic diversity and lower relative abundance of pro-inflammatory Sutterellaceae. Sutterellaceae was also significantly more abundant in patients who worsened, and Eggerthellaceae and Erysipelotrichaceae trended higher in patients who improved. Finally, PICRUSt2 functional predictions based on shifts in abundance of bacterial sequences repeatedly identified alterations in inositol degradation, which plays a key role in host immunomodulation, including inositol phospholipid signaling relevant to T-cell survival and proliferation. Our results bolster the paradigm of gut dysbiosis in CTCL and its functional implications in disease pathogenesis, and further delineate bacterial taxa associated with nbUVB response and with nbUVB treatment itself.

Narrowband ultraviolet B response in cutaneous T-cell lymphoma is characterized by increased bacterial diversity and reduced Staphylococcus aureus and Staphylococcus lugdunensis.

Skin microbiota have been linked to disease activity in cutaneous T-cell lymphoma (CTCL). As the skin microbiome has been shown to change after exposure to narrowband ultraviolet B (nbUVB) phototherapy, a common treatment modality used for CTCL, we performed a longitudinal analysis of the skin microbiome in CTCL patients treated with nbUVB. 16S V4 rRNA gene amplicon sequencing for genus-level taxonomic resolution, tuf2 amplicon next generation sequencing for staphylococcal speciation, and bioinformatics were performed on DNA extracted from skin swabs taken from lesional and non-lesional skin of 25 CTCL patients receiving nbUVB and 15 CTCL patients not receiving nbUVB from the same geographical region. Disease responsiveness to nbUVB was determined using the modified Severity Weighted Assessment Tool: 14 (56%) patients responded to nbUVB while 11 (44%) patients had progressive disease. Microbial α-diversity increased in nbUVB-responders after phototherapy. The relative abundance of Staphylococcus, Corynebacterium, Acinetobacter, Streptococcus, and Anaerococcus differentiated nbUVB responders and non-responders after treatment (q<0.05). Microbial signatures of nbUVB-treated patients demonstrated significant post-exposure depletion of S. aureus (q=0.024) and S. lugdunensis (q=0.004) relative abundances. Before nbUVB, responder lesional skin harboured higher levels of S. capitis (q=0.028) and S. warneri (q=0.026) than non-responder lesional skin. S. capitis relative abundance increased in the lesional skin of responders (q=0.05) after phototherapy; a similar upward trend was observed in non-responders (q=0.09). Post-treatment skin of responders exhibited significantly reduced S. aureus (q=0.008) and significantly increased S. hominis (q=0.006), S. pettenkoferi (q=0.021), and S. warneri (q=0.029) relative abundances compared to that of no-nbUVB patients. Staphylococcus species abundance was more similar between non-responders and no-nbUVB patients than between responders and no-nbUVB patients. In sum, the skin microbiome of CTCL patients who respond to nbUVB is different from that of non-responders and untreated patients, and is characterized by shifts in S. aureus and S. lugdunensis. Non-responsiveness to phototherapy may reflect more aggressive disease at baseline.

Nasal Dysbiosis in Cutaneous T-Cell Lymphoma Is Characterized by Shifts in Relative Abundances of Non-Staphylococcus Bacteria.

The nasal microbiome of patients with cutaneous T-cell lymphoma (CTCL) remains unexplored despite growing evidence connecting nasal bacteria to skin health and disease. Nasal swabs from 45 patients with CTCL (40 with mycosis fungoides, 5 with Sézary syndrome) and 20 healthy controls from the same geographical region (Chicago Metropolitan Area, Chicago, IL) were analyzed using sequencing of 16S ribosomal RNA and tuf2 gene amplicons. Nasal α-diversity did not differ between mycosis fungoides/Sézary syndrome and healthy controls (Shannon index, genus level, P = 0.201), but distinct microbial communities were identified at the class (R2 = 0.104, P = 0.023) and order (R2 = 0.0904, P = 0.038) levels. Increased relative abundance of the genera Catenococcus, Vibrio, Roseomonas, Acinetobacter, and unclassified Clostridiales was associated with increased skin disease burden (P < 0.005, q < 0.05). Performed to accurately resolve nasal Staphylococcus at the species level, tuf2 gene amplicon sequencing revealed no significant differences between mycosis fungoides/Sézary syndrome and healthy controls. Although S. aureus has been shown to worsen CTCL through its toxins, no increase in the relative abundance of this taxon was observed in nasal samples. Despite the lack of differences in Staphylococcus, the CTCL nasal microbiome was characterized by shifts in numerous other bacterial taxa. These data add to our understanding of the greater CTCL microbiome and provide context for comprehending nasal-skin and host‒tumor‒microbial relationships.

Drug-induced acne with elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis.

Elexacaftor/tezacaftor/ivacaftor (ELX-TEZ-IVA) is a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator shown to improve lung function and reduce sweat chloride in people with Cystic Fibrosis (CF). The only commonly reported dermatologic adverse effect with CFTR modulators including ELX-TEZ-IVA is rash. In this case series, we describe 19 patients who reported new onset or worsening of acne after initiation of this drug to their CF pharmacist or another member of their CF care team. The mechanism and frequency of this adverse effect is unknown.

Cutaneous Bacillary Angiomatosis in a Renal Transplant Patient.

A 37-year-old man with a history of renal transplantation in 2013 due to focal segmental glomerulosclerosis presented to the emergency room with a 2-week history of fever, chills, anorexia, weight loss, abdominal pain, diarrhea, and a new asymptomatic lesion on the right side of the neck. The patient worked as a truck driver and frequently traveled to Wisconsin; he had not traveled internationally in the past year. He lived with his brother who had a pet cat. He was compliant with his anti-rejection medication regimen, which included mycophenolate mofetil, tacrolimus, and prednisone. Physical examination of the neck revealed an 8-mm exophytic, friable, red papule with overlying blood crusts (Figure 1). The remainder of the mucocutaneous examination was unremarkable, and there was no palpable lymphadenopathy. The patient was started on empiric intravenous cefepime and metronidazole and admitted to the hospital for further management. A punch biopsy of the lesion was performed.

Pruritus in Cutaneous T-Cell Lymphoma and Its Management.

Pruritus is a common symptom in cutaneous T-cell lymphoma (CTCL) and critically affects the quality of life of patients. Understanding the pruritogenesis has led to development of new therapeutic agents with promising outcomes in management of this recalcitrant symptom. Clinical assessments are warranted to aid in evaluation of treatment response or disease recurrence. Severe pruritus scores may require further investigation of emotional distress for a better patient approach. Dermatologists play a key role in the treatment of CTCL-pruritus by guiding the patient in the importance of preserving the integrity of the skin barrier.

Hemophagocytic Lymphohistiocytosis in Cutaneous T-Cell Lymphoma.

Importance: Hemophagocytic lymphohistiocytosis (HLH) has been reported as a serious complication of cutaneous T-cell lymphoma (CTCL). Despite available diagnostic guidelines, it remains a diagnostic and therapeutic challenge in this patient population. Objectives: To examine the characteristics of CTCL associated with HLH and analyze the presenting signs and symptoms, therapeutic options, and outcome. Design, Setting, and Participants: In this case series, patients diagnosed with CTCL and HLH who were treated at a single institution from January 1, 2014, through December 31, 2017, were studied. Exposures: The HLH-2004 trial criteria, HScore, and various clinical and histopathologic variables were applied to and analyzed in the cohort. Main Outcomes and Measures: Subtype of CTCL, treatment administered for HLH, and patient outcome were assessed. Results: Seven patients (4 men and 3 women; median age, 50 years; range, 34-77 years) were identified from the database and included in the study. Cytotoxic subtypes of CTCL that involve the deep dermis and subcutaneous tissue were most commonly associated with HLH. Four patients met 5 or more HLH-2004 trial criteria, and 5 had an HScore probability greater than 85% at presentation. Common presenting HLH symptoms were fever and malaise. Cyclosporine, polychemotherapy, and systemic corticosteroids were the most common treatments. Patients receiving allogeneic stem cell transplants had the best outcomes, with all 3 of these patients alive and in complete remission. Conclusions and Relevance: Hemophagocytic lymphohistiocytosis is a life-threatening complication of CTCL associated with rare cytotoxic CTCL subtypes that primarily involve the subcutaneous tissue. Because these cases may resemble a granulomatous or infectious condition, the diagnosis and appropriate management are often delayed. The results of this study demonstrate the need for high awareness of HLH in patients with panniculitic lymphomas and indicate that allogeneic stem cell transplantation may be the best option for a sustained remission.