Interstitial mycosis fungoides: A rare presentation of mycosis fungoides with overlapping granulomatous and folliculotropic features.

BACKGROUND: Interstitial mycosis fungoides (IMF) is a rare subtype of mycosis fungoides (MF) characterized by atypical lymphocytes infiltrating the reticular dermis between collagen bundles with limited epidermotropism and variable granulomatous features. METHODS: Retrospective single institution review of 31 cases of IMF including clinical characteristics, disease course and pathological features. RESULTS: Our cohort was predominately male (19; 61%, M:F 1.6:1) with a mean age at diagnosis of 43 years (range 11-85), mean signs/symptoms duration of 7 years prior to diagnosis, and 6 years mean follow-up duration. Clinically, patients often exhibited symmetric ill-defined patches/plaques involving intertriginous regions with tan-yellow hyperpigmentation and follicular-based papules, wrinkling, and alopecia. Lymphadenopathy was noted in seven patients. Fifteen (52%) patients were in near or complete clinical remission at the latest follow-up. T-cell receptor gene rearrangement was positive in 23/24 (96%) cases. Histopathologically, atypical cells were small-medium, CD4+ (29; 94%) or rarely CD4+/CD8+ (1; 3%) lymphocytes infiltrating the reticular dermis with thickened collagen bundles (27; 87%), multinucleated giant cells (12; 39%), and often tracing along adnexa with subtle folliculotropism (12/20; 60%). CONCLUSIONS: Our study demonstrates IMF is an indolent subtype of MF with distinct features, including frequent granulomatous and subtle follicular involvement resulting in alopecia.

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.

Ocular manifestations of vitiligo: a systematic review.

Vitiligo is a disorder characterized by loss of epidermal melanocytes, resulting in depigmented macules and patches. While the relationship between ocular pathology and vitiligo has been demonstrated in conditions such as Vogt-Koyanagi-Harada and Alezzandrini syndromes, the ocular associations of non-syndromic vitiligo are incompletely understood. We conducted a systematic review to comprehensively describe the structural and functional changes seen in the eyes of patients with vitiligo, to identify patients at heightened risk for ocular disease, and to provide an approach to management of ocular manifestations of vitiligo. Overall, the strongest link between vitiligo and ocular pathology seems to lie with dry eye disease and pigmentary abnormalities of various ocular structures, especially the retinal pigment epithelium. Normal-tension glaucoma may also be more prevalent in the vitiligo population. The available literature did not provide conclusive evidence for increased risk of cataracts or uveitis. Aside from the impact of symptomatic dry eye disease, it seems unlikely that there are significant functional consequences of these ocular manifestations such as impaired visual acuity or visual fields.

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.

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).

Ocular findings in vitiligo and recommendations for dermatologists.

Since extracutaneous melanocytes in the eye may also be affected in vitiligo, a systematic review was conducted to explore the ocular manifestations of vitiligo. Studies point to a higher risk of ocular findings in periorbital vitiligo. Dry eye disease is the most reported ocular abnormality in vitiligo. Additionally, several small studies have found potential links to uveitis and glaucoma. Various other chorioretinal pigmentary changes are also reported, but without accompanying functional consequences or changes in vision. Although there is a need for larger studies to further elucidate these associations, dermatologists should be aware of potential ocular comorbidities in vitiligo and refer to ophthalmology accordingly.

Disease-Defining Molecular Features of Primary Cutaneous B-Cell Lymphomas: Implications for Classification and Treatment.

Primary cutaneous B-cell lymphoma-primary cutaneous follicle center lymphoma; primary cutaneous marginal zone lymphoma; and primary cutaneous diffuse large B-cell, leg type-is a heterogeneous group with a variety of clinical and histological presentations. Until recently, the molecular bases of these disease subtypes have been unclear. We and others have identified the specific genetic characteristics that distinguish these subtypes from their respective systemic counterparts. These molecular features can improve diagnoses, determine the likelihood of concurrent or future systemic disease, and enable the rational design of novel clinical trials.

Lifestyle, demographic and Skindex measures associated with cutaneous T-cell lymphoma: a single institution cohort study.

Cutaneous T-cell lymphoma (CTCL) risk factors and associated quality of life are poorly understood. Previous studies of CTCL risk factors explored patient comorbidities and lifestyle exposures, but not in conjunction with disease stage, subtype, severity, or health-related quality of life (HRQoL). We investigated lifestyle exposures and demographic factors associated with advanced-stage disease, increased disease severity, and poorer HRQoL outcomes in this single-center cohort study. A cohort survey study was conducted at Northwestern's Multidisciplinary Cutaneous Lymphoma specialty clinic between April 2019 and June 2021. REDCap surveys were administered to 140 patients with CTCL, investigating patients' demographics, lifestyle and chemical exposures. QoL was evaluated using the Skindex survey; pain and itch with ten-point Likert scales. Modified Severity Weighted Assessment Tool (mSWAT), disease stage, and disease subtype were confirmed upon enrollment in the study by a single board-certified dermatologist specializing in CTCL. Factors were compared by t test or Fischer's exact test. Median age was 63 years (range 14-92) with male-to-female ratio of 1.2:1. The most common diagnosis was CD4 + MF (n = 94, 67.1%). Common lifestyle exposures included smoking (past or current) (52.3%) and chemical exposure history (all sources [53.7%]; industrial only [33.0%]). History of chemical exposures were associated with advanced stage disease (p = 0.003) and worse QoL outcomes (p = 0.001). There were significant racial differences, respectively, in early (I-IIA) vs late (IIB-IV) stage disease (p = 0.003). Obesity, hygiene, smoking, recent sun exposure, education and atopy were not significantly associated with disease stage or severity. We provide an analysis of lifestyle and demographic factors in the context of CTCL disease severity, stage, and HRQoL. We identified race as a potential risk factor for advanced stage disease and both skin phototype and chemical exposures as a risk factor for increased disease severity as measured by mSWAT. QoL outcomes were multifactorial and significantly associated with history of chemical exposure, severe pain/itch, race, disease stage and subtype. An improved understanding of these associations may lead to better individualized care. As chemical exposure and race were found to be significant factors associated with advanced-stage disease, taking exposure histories and addressing racial disparities may improve care for CTCL patients.

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.

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.

Fibroids and Urinary Symptoms Study (FUSS).

OBJECTIVE: The aims of the study were to characterize pelvic floor and urinary symptoms in women seeking treatment for uterine fibroids and to explore the association between uterine/fibroid size and pelvic floor symptoms. METHODS: Women seeking treatment for uterine fibroids at a single academic center were enrolled in this cross-sectional study. All participants underwent pelvic imaging and completed the Symptom Severity Subscale of the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) and the Pelvic Floor Distress Inventory (PFDI-20). RESULTS: One hundred ninety-five women with a mean age of 41 ± 6 years and body mass index of 29 ± 7 kg/m2 were included. In this cohort, 58% identified as Black and 38% had at least 1 vaginal delivery. Women attributed pelvic pain (68%), dyspareunia (37%), and urinary incontinence (31%) to their fibroids. The mean ± SD UFS-QOL score was 48.7 ± 25.4, and 63% of participants reported being at least "somewhat bothered" by tightness/pressure in pelvic area, 60% by frequent daytime urination, and 47% by nocturia. The mean PFDI-20 score was 45.5 ± 31.9. Women reported being at least "somewhat bothered" by heaviness/dullness in the pelvis (60%), frequent urination (56%), pelvic pain or discomfort (48%), and sensation of incomplete bladder emptying (43%). The PFDI-20 and UFS-QOL scores were not correlated with uterine volume (r = 0.12, P = 0.12, and r = 0.06, P = 0.44) or fibroid size (r = 0.09, P = 0.26, and r = 0.01, P = 0.92). CONCLUSIONS: Women presenting for evaluation and treatment of fibroids report high rates of pelvic floor symptoms, particularly urinary frequency and pelvic pressure. However, uterine size and fibroid size are not associated with pelvic floor symptom bother.

A cell autonomous torsinA requirement for cholinergic neuron survival and motor control.

Cholinergic dysfunction is strongly implicated in dystonia pathophysiology. Previously (Pappas et al., 2015;4:e08352), we reported that Dlx5/6-Cre mediated forebrain deletion of the DYT1 dystonia protein torsinA (Dlx-CKO) causes abnormal twisting and selective degeneration of dorsal striatal cholinergic interneurons (ChI) (Pappas et al., 2015). A central question raised by that work is whether the ChI loss is cell autonomous or requires torsinA loss from neurons synaptically connected to ChIs. Here, we addressed this question by using ChAT-Cre mice to conditionally delete torsinA from cholinergic neurons ('ChAT-CKO'). ChAT-CKO mice phenocopy the Dlx-CKO phenotype of selective dorsal striatal ChI loss and identify an essential requirement for torsinA in brainstem and spinal cholinergic neurons. ChAT-CKO mice are tremulous, weak, and exhibit trunk twisting and postural abnormalities. These findings are the first to demonstrate a cell autonomous requirement for torsinA in specific populations of cholinergic neurons, strengthening the connection between torsinA, cholinergic dysfunction and dystonia pathophysiology.