Primary cutaneous lymphoma: recommendations for clinical trial design and staging update from the ISCL, USCLC, and EORTC.

The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.

Real-world study on the use of pegylated interferon alpha-2a for treatment of mycosis fungoides/Sézary syndrome using Time to Next Treatment as a measure of clinical benefit: An EORTC CLTG study.

INTRODUCTION: Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic malignant diseases that typically necessitate diverse strategies to achieve remission. Systemic interferon alpha (IFN-α, subtypes 2a and 2b) has been used for MF/SS since 1984, however its production was recently stopped and so the recombinant pegylated (PEG) form of IFN α-2a remains as single IFN alternative treatment, even though not approved for MF/SS. OBJECTIVE: To assess effectiveness and safety of PEG IFN α-2a in monotherapy and in combination with other treatments using time to next treatment (TTNT) as a measure of clinical therapeutic benefit in real world setting. METHODS: We conducted an international and multicenter retrospective study of patients with MF and SS at any stage, treated with PEG IFN α-2a, from July 2012 to February 2022. Patients were included across 11 centers in 10 countries. Primary endpoints were to determine TTNT of PEG IFN α-2a and the adverse events (AE) in MF/SS. RESULTS: In total 105 patients were included, mean age was 61 (22-86 years); 42 (40%) with disease stage IA-IIA, 63 (60%) with stage IIB-IVB. PEG IFN α-2a was combined with other therapies in 67 (64%) patients, usually with extracorporeal photopheresis (36%) and bexarotene (22%). Fifty-seven percent of stage I-IIA patients achieved ORR, whereas 51% of stage IIB-IVB. Combination therapy showed a TTNT of 10.4 months, while 7 months in monotherapy (p=0.0099). Overall, TTNT was 9.2 months, ORR was 53% (56/105), CR and PR were 13% and 40%, respectively.AE were described in 69% (72) of the patients. Flu-like symptoms (27%), lymphopenia (23%) and elevated liver function (10%) were the most frequently reported. Grade 3-4 adverse events were reported in 23 (21%) patients, which were mostly related to myelosuppression. LIMITATIONS: retrospective data analysis and unrestricted number of combination therapies. CONCLUSIONS: PEG IFN α-2a for MF/SS showed ORR of 53%, TTNT of 9.2 months, superiority of combination regimens in comparison to monotherapy and doses of 180 mcg/weekly related to higher ORR.

Paediatric onset lymphomatoid papulosis: results of a multicentre retrospective cohort study, on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG).

BACKGROUND: Lymphomatoid Papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population is scarce. OBJECTIVES: To characterize epidemiological, clinical, histopathological, and prognostic features of paediatric LyP. METHODS: This was a retrospective, multicentre international cohort study including 87 cases of children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years old at disease onset were included. Diagnosis was made in each centre based on clinical-pathological correlation. RESULTS: Eighty-seven patients from 12 centres were included. The mean age at onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2:1. The mean time between onset of first cutaneous lesions and diagnosis was 1.3 years (range 0-14 years). Initial misdiagnosis concerned 26.4% of patients. Initially, LyP was most often misdiagnosed as Pityriasis lichenoides et varioliformis acuta (PLEVA), insect bites, or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned for 20.7% of patients. The main histological subtype was type A in 55.1% of the cases. If analysed, monoclonal TCR rearrangement was found in 76.5% of the skin biopsies. The overall survival rate was 100% with follow up at 5 years available for 33 patients and at 15 years for 8 patients. A development of associated haematological malignancy (HM) occurred in 9.6% of the cases (7/73), including four mycosis fungoides (MF) cases, one primary cutaneous anaplastic large cell lymphoma (pc-ALCL), one systemic ALCL and one case of acute myeloid leukaemia. If we compare incidence rates of cancer with the world 0-19 years old population from 2001-2010, we estimate a significantly higher risk of associated malignancy in general, occurring before the age of 19 years old with incidence rate ratio of 87.49 (CI 86.01-88.99). CONCLUSIONS: We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall the prognosis of the disease is good, with excellent survival rates for all patients. Due to increased risk of associated HM, a long-term follow-up should be recommended for LyP patients.

Bacterial Skin Dysbiosis in Darier Disease.

INTRODUCTION: Darier disease is a rare inherited disease with dominant skin manifestations including keratotic papules and plaques on sebaceous and flexural areas. Secondary infection of skin lesions is common, and Staphylococcus aureus commonly colonizes these lesions. The aim of the study was to characterize the bacterial microbiome of cutaneous Darier lesions compared to normal-looking skin and disease severity. METHODS: All patients with a history of Darier followed up at Emek Medical Center were invited to participate in the study. Patients that did not use antibiotics in the past month and signed informed consent had four skin sites sampled with swabs: scalp, chest, axilla, and palm. All samples were analyzed for bacterial microbiome using 16S rDNA sequencing. RESULTS: Two hundred and eighty microbiome samples obtained from lesional and non-lesional skin of the scalp, chest, axilla, and palm of 42 Darier patients were included in the analysis. The most abundant bacterial genera across all skin sites were Propionibacterium, Corynebacterium, Paracoccus, Micrococcus, and Anaerococcus. Scalp and chest lesions featured a distinct microbiome configuration that was mainly driven by an overabundance of Staphylococci species. Patients with more severe disease exhibited microbiome alterations in the chest, axilla, and palm compared with patients with only mild disease, driven by Peptoniphilus and Moryella genera in scalp and palmar lesions, respectively. CONCLUSION: Staphylococci were significantly associated with Darier lesions and drove Darier-associated dysbiosis. Severity of the disease was associated with two other bacterial genera. Whether these associations also hold a causative role and may serve as a therapeutic target remains to be determined and requires further investigation.

A Comparison of Hidradenitis Suppurativa Characteristics Among Israeli Arabs and Jews: Analysis of Two Cohorts.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving apocrine gland-bearing regions. There is an under-representation of non-Caucasians in epidemiologic studies of HS. The characteristics of HS in Israeli Arabs have not yet been studied. OBJECTIVES: To investigate the demographic and clinical profile of HS in the Israeli Arab population. METHODS: A retrospective analysis was conducted in two cohorts of patients with HS in Israel. The patients were derived from the database of a large health management organization (n=4191, 639 Arabs; population-based) and a major tertiary medical center (n=372, 49 Arabs). Demographic and clinical data were compared between ethnic groups. RESULTS: The prevalence of HS in Israeli Arabs was found to be 0.5%, fivefold higher than in Jews. Arab patients were younger (35.3 vs. 40.5 years, P < 0.001) and mostly male (52% vs. 35.7%, P < 0.001), with lower rates of co-morbidities, including smoking (40.8% vs. 55.7%, P < 0.001), hyperlipidemia, and depression as well as a higher rate of dissecting cellulitis (10.2% vs. 1.9%, P = 0.008). HS was more severe in Arabs, but of shorter duration, with mainly axillary involvement (79.6% vs. 57.9%, P = 0.004). Treatment with hormones was more common in Jews, and with biologic agents in Arabs. CONCLUSIONS: The findings suggest a different phenotype of HS in Arabs, warranting further study.

Mycosis Fungoides in Solid-Organ Transplant Recipients: A Multicenter Retrospective Cohort Study.

BACKGROUND: Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics. OBJECTIVE: The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy. METHODS: A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022. RESULTS: Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5-22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA - 4, IB - 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1-8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB - 4, III - 1). CONCLUSIONS: MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up.

Association between Hidradenitis Suppurativa and Abnormalities in Semen Parameters and Sexual Function: A Pilot Study.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting patients of reproductive age. Although HS shares risk factors with male infertility, only 1 epidemiological study has evaluated this association. To further evaluate this potential association, findings on semen and hormonal analysis, testicular ultrasound, and the International Index of Erectile Function (IIEF-15) were compared between 28 men attending a tertiary HS clinic during the period April 2019 to April 2021, and 44 healthy controls, spouses of infertile women undergoing semen evaluation before in vitro fertilization. Patients with HS were divided based on the absence or presence of gluteal and genital lesions. Patients with HS were younger than controls (median 27 vs 34 years, p < 0.0004) and had a higher proportion of smokers (86% vs 33%, p < 0.0001). Semen parameters in patients with gluteal-genital lesions, specifically those with severe scrotal involvement necessitating surgery, were lower than the WHO reference values and significantly lower than in patients without gluteal-genital lesions and controls. Erectile dysfunction was reported by 93% of patients with HS. These findings suggest that spermatogenesis and sexual function may be impaired in young men with HS. Therefore, multidisciplinary management of HS should include their evaluation to identify patients who might benefit from semen cryopreservation and sexual treatment.

Identifying unmet needs and challenges in the definition of a plaque in mycosis fungoides: An EORTC-CLTG/ISCL survey.

BACKGROUND: Consensus about the definition and classification of 'plaque' in mycosis fungoides is lacking. OBJECTIVES: To delineate a comprehensive view on how the 'plaque' entity is defined and managed in clinical practice; to evaluate whether the current positioning of plaques in the TNMB classification is adequate. METHODS: A 12-item survey was circulated within a selected panel of 22 experts (pathologists, dermatologists, haematologists and oncologists), members of the EORTC and International Society for Cutaneous Lymphoma. The questionnaire discussed clinical and histopathological definitions of plaques and its relationship with staging and treatment. RESULTS: Total consensus and very high agreement rates were reached in 33.3% of questions, as all panellists regularly check for the presence of plaques, agree to evaluate the presence of plaques as a potential separate T class, and concur on the important distinction between plaque and patch for the management of early-stage MF. High agreement was reached in 41.7% of questions, since more than 50% of the responders use Olsen's definition of plaque, recommend the distinction between thin/thick plaques, and agree on performing a biopsy on the most infiltrated/indurated lesion. High divergence rates (25%) were reported regarding the possibility of a clinically based distinction between thin and thick plaques and the role of histopathology to plaque definition. CONCLUSIONS: The definition of 'plaque' is commonly perceived as a clinical entity and its integration with histopathological features is generally reserved to specific cases. To date, no consensus is achieved as for the exact definition of thin and thick plaques and current positioning of plaques within the TNMB system is considered clinically inadequate. Prospective studies evaluating the role of histopathological parameters and other biomarkers, as well as promising diagnostic tools, such as US/RM imaging and high-throughput blood sequencing, are much needed to fully integrate current clinical definitions with more objective parameters.

Mammalian target of rapamycin inhibitors for prolonged secondary prevention of nonmelanoma skin cancer in solid organ transplant recipients.

Immunosuppressive agents are essential for graft survival in solid-organ transplant recipients (SOTRs), but they have substantial durable side effects, including a higher incidence of aggressive nonmelanoma skin cancers (NMSCs). Hitherto, only one class of immunosuppressants, mammalian target of rapamycin inhibitors (mTORi), may inhibit skin tumor formation, however their durable effectiveness is controversial. To evaluate the sustained effectiveness of mTORi in reducing NMSCs' incidence in SOTRs, a retrospective study was conducted in a specialized dermatology clinic for SOTRs of a tertiary university-affiliated medical center. SOTRs with a history of at least one histologically proven NMSC were followed for 6 years: 3 years after transplantation, before initiation of mTORi, and 3 years under mTORi treatment. The cohort consisted of 44 SOTRs. Treatment with mTORi was initiated on average 6.27 (3.34-6.34) years following transplantation. In the 3 years before mTORi treatment initiation, the mean number of new NMSCs per patient was 2.11 (1-14). This value decreased to 1.2 (0-19) in the 3 years under mTORi treatment (p = 0.0007). Analysis by NMSC type yielded a significant decrease in both SCCs and BCCs. This study found that mTORi are effective for prolonged secondary prevention of NMSCs in SOTRs.

Early rituximab treatment is associated with increased and sustained remission in pemphigus patients: A retrospective cohort of 99 patients.

Rituximab is the front-line therapy for pemphigus disease. Although very effective, relapse rates are high. We assessed factors associated with disease remission and early relapse following the first rituximab cycle. A single center, retrospective cohort study of patients with pemphigus treated with rituximab (1000 mg 0, 14 days) at the Autoimmune Bullous Disease Clinic of the Division of Dermatology in Rabin Medical Center, Israel, between January 1, 1995 and March 31, 2020. The cohort included 99 patients with a median follow-up of 37 months (range 12-155). After a single rituximab cycle, 74 patients (75%) achieved remission. Increased time to rituximab was associated with decreased remission rates (OR, 0.98 per month; 95% CI, 0.97-0.998). Of patients in remission with sufficient follow-up, 15/69 (22%) experienced an early relapse (≤12 months from remission). Prolonged time to rituximab and increased baseline disease severity, were associated with early relapse (OR, 1.02 per month; 95% CI, 1.001-1.04; OR, 1.04 per point; 95% CI, 1.01-1.08, accordingly). Initiating rituximab early following diagnosis is recommended. Maintenance rituximab infusions, especially for patients with severe baseline disease, should be further investigated.

Treating pediatric cutaneous Leishmania tropica with systemic liposomal amphotericin B: A retrospective, single-center study.

Leishmania tropica (L. tropica) cutaneous leishmaniasis (CL) is associated with high morbidity and low response rate to therapy, especially in pediatric patients. Intravenous (IV) liposomal amphotericin B (LAmB) has been used off-label as a treatment for L. tropica CL for many years. However, data regarding its efficacy and safety in children is lacking. In order to evaluate the efficacy and safety of IV LAmB for treating pediatric patients with L. tropica, we retrospectively reviewed electronic medical records of 24 children who were diagnosed with L. tropica CL and treated with IV LAmB during 2014-2020, at a tertiary medical center in Israel. Fourteen (58%) completed the treatment protocol and 10 (42%) experienced an infusion-related adverse event (IRAE) leading to treatment termination. Complete response was noted in 6/14 (43%) patients, while 8/14 (57%) failed to respond. Lower response rate was noted in lesions involving the mid-facial area. The relatively low response rate is speculated to result from a low dose of LAmB, short follow-up period, and difficult to treat anatomic locations. The observation of a lower response rate for mid-facial lesions should be validated in larger cohorts. The highrisk of IRAE should be considered in physician decisions regarding this treatment.

Low-Dose Acitretin for Secondary Prevention of Keratinocyte Carcinomas in Solid-Organ Transplant Recipients.

BACKGROUND: Keratinocyte carcinomas, particularly squamous cell carcinoma (SCC), occur more frequently and aggressively in solid-organ transplant recipients (SOTRs) than in the general population. Systemic retinoids are effective in secondary prevention of keratinocyte carcinomas in this population, but their use is limited by adverse effects including a rebound effect in cases of treatment discontinuation. OBJECTIVE: Our aim was to determine whether low-dose acitretin is efficient in the secondary prevention of keratinocyte carcinomas in SOTRs. METHODS: This retrospective case-crossover study was conducted at a specialized dermatology clinic for SOTRs in a large transplantation center in 2010-2017. Patients with at least 1 previous keratinocyte carcinoma who were treated with acitretin 10 mg/day for 2 years were included. The main outcome was the difference in the number of new keratinocyte carcinomas diagnosed during treatment compared to during the 2-year pretreatment period. RESULTS: The cohort included 34 SOTRs. A significant reduction in the mean number of new keratinocyte carcinomas during treatment relative to the pretreatment period was observed (1.7 vs. 3.6, -53% p = 0.002). Similar results were noted on analysis by tumor type, for both SCC and basal cell carcinoma. CONCLUSION: This study of SOTRs demonstrated positive results for low-dose acitretin as a chemoprevention of keratinocyte carcinomas in this population.

New Insights into Macular Type of Primary Cutaneous B-Cell Lymphoma: Extension of the Clinical and Histopathological Patterns.

BACKGROUND: Primary cutaneous B-cell lymphoma (PCBCL) classically presents with papules, plaques, and nodules/tumors. Previous reports of PCBCL manifesting with macular lesions are scarce and focused on primary cutaneous follicle-center cell lymphoma (PCFCL). OBJECTIVES: The objective of this study was to report our experience with PCBCL presenting with erythematous macules. METHODS: Patients with low-grade PCBCL manifesting with erythematous patches, diagnosed and managed between January 2000 through December 2019 at 2 tertiary cutaneous-lymphoma outpatient clinics, were included. Clinical data were retrospectively collected, and biopsy specimens of the macules, and if present of the typical nodular/tumoral lesions, were reviewed. RESULTS: There were 14 patients, aged 16-67 years, 8 had PCFCL and 6 marginal zone lymphoma (PCMZL). All had 1-15 cm erythematous macules, mimicking: interstitial granuloma annulare/vascular tumors/early-stage folliculotropic mycosis fungoides, or presenting with figurate erythema or livedo reticularis-like/net-like pattern. In 3 patients, macules were the presenting lesions, in 2 as the sole manifestation, whereas in 12 patients, typical PCBCL lesions were observed during disease course. The macules showed in all, superficial and deep perivascular infiltrates, and in most, periadnexal infiltrates. Micronodules were observed in 11 specimens, with nodular infiltrates also observed in 4. B cells comprised the majority of the lymphocytes in only 4. Seven of 11 cases tested showed immunoglobulin heavy chain monoclonality. CONCLUSIONS: PCMZL and PCFCL may manifest with erythematous macules. Physicians should be aware of this unusual manifestation of low-grade PCBCL, which may represent a clinicopathological diagnostic pitfall.

Post hoc Analysis of a Randomized, Controlled, Phase 2 Study to Assess Response Rates with Chlormethine/Mechlorethamine Gel in Patients with Stage IA-IIA Mycosis Fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma. Patients can be treated using chlormethine gel, a skin-directed therapy developed and approved for MF. In the randomized, controlled 201 trial, chlormethine gel was found to be noninferior to equal-strength chlormethine ointment. However, there remains a need to gain more insight into outcome measures after treatment. OBJECTIVE: The aim of this study was to further investigate the potential of chlormethine gel treatment through a novel post hoc analysis of the 201 trial data (NCT00168064). METHODS: Patients were randomized to chlormethine gel or ointment; response assessments included Composite Assessment of Index Lesion Severity (CAILS) and total body surface area (BSA). In this post hoc analysis, additional subgroup response analyses were performed for stage IA/IB-IIA MF. Very good partial response (75 to <100% improvement) was included as an additional response category. Time to response and overall response trends were determined. Finally, multivariate time-to-event analyses were performed to determine whether associations were observed between treatment frequency, response, and adverse events. RESULTS: Response rates were significantly higher for patients with stage IA MF for CAILS (intent-to-treat [p = 0.0014] and efficacy-evaluable [EE; p = 0.0036] populations) and BSA (EE population [p = 0.0488]) treated with gel versus ointment. Time to first CAILS response and response trends were better for all-stage gel-treated patients overall. No association was seen between treatment frequency and response or occurrence of adverse events at the following visit. An association was observed between the occurrence of contact dermatitis and improved clinical response at the next visit (p = 0.0001). CONCLUSION: This post hoc analysis shows that treatment with chlormethine gel may result in higher and faster response rates compared with chlormethine ointment, which confirms and expands results reported in the original analysis. The incidence of contact dermatitis may potentially be a prognostic indicator for clinical response; this needs to be confirmed in a larger population.

The Bacteriology of Skin Lesions in Patients with Hidradenitis Suppurativa Is Associated with Previous Antibiotic Treatment in the Community Setting: A Referral Center Experience.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic skin disease characterized by inflammatory nodules and abscesses. The pathogenic role of bacteria is not fully understood. As the diagnosis is usually delayed, patients are often treated with several lines of antibiotics in a nonstandardized fashion. The aim of the study was to investigate and compare the bacteriology of active HS lesions in patients treated or not treated with antibiotics in the community setting before referral to a dedicated HS clinic. METHODS: Purulent skin lesions of patients with HS referred to the HS Clinic of Rabin Medical Center in 2009-2020 were cultured. Data were collected from the patients' medical files and microbiology reports. The correlation between the location of the skin lesion and the bacteriologic profile was analyzed, and the effects of previous antibiotic treatment on the bacteriologic profile of the lesions and susceptibility patterns of the cultured bacteria were evaluated. RESULTS: Pus (or tissue) from inflammatory lesions of 97 patients with HS was cultured. Mean (SD) patient age was 39.5 (13.0) years, and mean delay in diagnosis was 7.3 (8.3) years. Most patients (57.7%) had dominant involvement of one location, with the most active lesions concentrated in the genitalia, gluteal/perineal area, and axilla. Enterobacterales species were the most frequent isolates detected in all locations except the face and scalp. Seventy-eight patients (80.4%) had been treated in the community setting prior to referral with a median (range) of 2 (1-8) lines of antibiotics. The most commonly prescribed antibiotics were amoxicillin/clavulanate (22.0%), doxycycline/minocycline (16.8%), clindamycin (16.2%; monotherapy 8.1%, clindamycin with rifampicin 8.1%), and cephalexin (13.9%). Compared to the previously untreated patients, cultures of lesions from the previously treated patients yielded a higher percentage of gram-negative Enterobacterales (the most common isolates in this group) (31.3% vs. 10.3%) and a significantly higher median number of isolates per culture (2 vs. 1, p < 0.0001). Gram-positive bacteria, usually considered contaminants (mainly coagulase-negative staphylococci) accounted for 31.0% of the isolates in the previously treated group. Susceptibility testing for the entire cohort revealed 100% bacterial sensitivity to ciprofloxacin. Staphylococcus spp. were 100% sensitive to rifampicin. Both gram-positive and gram-negative bacteria had high sensitivity to trimethoprim and sulfamethoxazole. CONCLUSION: Nonstandardized antibiotic treatment of HS in the community setting can skew the microbiology of skin lesions toward gram-negative bacteria. Therefore, treatment with trimethoprim and sulfamethoxazole or ciprofloxacin, either alone or combined with rifampicin, may be considered.

Hidradenitis Suppurativa International Online Community: Patient Characteristics and a Novel Model of Treatment Effectiveness.

Treatment for hidradenitis suppurativa is diverse, yet frequently unsatisfactory. The aims of this study were to create a reproducible artificial intelligence-based patient-reported outcome platform for evaluation of the clinical characteristics and comorbidities of patients with hidradenitis suppurativa, and to use this to grade treatment effectiveness. A retrospective patient- reported outcome study was conducted, based on online questionnaires completed by English-speaking patients registered to the hidradenitis suppurativa StuffThatWorks® online community. Data collected included patient characteristics, comorbidities and treatment satisfaction. These were recoded into scalable labels using a combination of machine learning algorithm, manual coding and validation. A model of treatment effectiveness was generated. The cohort included 1,050 patients of mean ± standard deviation age 34.3 ± 10.3 years. Greater severity of hidradenitis suppurativa was associated with younger age at onset (p < 0.001) and male sex (p < 0.001). The most frequent comorbidities were depression (30%), anxiety (26.4%), and polycystic ovary syndrome (16.6%). Hurley stage I patients rated topical agents, dietary changes, turmeric, and pain relief measures more effective than tetracyclines. For Hurley stage II, adalimumab was rated most effective. For Hurley stage III, adalimumab, other biologic agents, systemic steroids, and surgical treatment were rated more effective than tetracyclines. Patients with hidradenitis suppurativa often have comorbid psychiatric and endocrine diseases. This model of treatment effectiveness provides a direct comparison of standard and complementary options.

Efficacy and safety of a thermal fractional skin rejuvenation system (Tixel) for the treatment of facial and/or scalp actinic keratoses.

Actinic keratoses are common cutaneous lesions with a potential to progress to invasive squamous cell carcinoma. Therefore, treatment is crucial. The Tixel® is a noninvasive thermomechanical device designed to transfer heat to the upper dermis in a controlled manner according to a predetermined setting. This study aimed to evaluate the safety and efficacy of a thermomechanical fractional skin resurfacing technology for the treatment of facial and scalp actinic keratoses. A prospective, open-label, before-after study was conducted in a tertiary medical centre from May 2020 to April 2021. Patients presenting with facial/scalp actinic keratoses of mild-to-moderate thickness underwent 2 or 3 Tixel treatments (depending on clinical improvement), 3-4 weeks apart. The reduction in lesion count and overall improvement in appearance were assessed by clinical examination and digital photography. Findings were compared between baseline and follow-up at 3 months after the last treatment session. Patient satisfaction was evaluated by questionnaire, and adverse effects were documented. A total of 20 patients participated in the study. All completed 2-3 treatments and follow-up visits. Assessment of digital photographs was performed by 2 assessors blinded to the timepoint at which each photo was taken (before or after treatment). The average number of lesions at baseline was 9.8 (± 4.8) and the mean reduction in lesion count was 7.9 (± 4.4) (80.6%). Complete clearance was observed in 31.6% of patients. No adverse effects were noted during treatment and follow-up. Most patients reported being "very satisfied" or "satisfied" with the treatment results (85%) and experience (95%). Treating facial and scalp actinic keratoses with the Tixel device was found to be effective and safe.

The Risk of Internal Malignancy Following a Prior Diagnosis of Non-Melanoma Skin Cancer in Solid Organ Transplant Recipients.

BACKGROUND: Solid organ transplant recipients (SOTRs) are at increased risk for both skin and internal malignancies (IM). The risk of IM after the occurrence of non-melanoma skin cancer (NMSC) has been studied in the general population but very little is known about this association in SOTRs. OBJECTIVES: To evaluate the risk of IM following a prior diagnosis of post transplantation NMSC in SOTRs. METHODS: This single center retrospective cohort study included a study population of 329 SOTRs from Rabin Medical Center who had a post-transplant diagnosis of skin malignancy, internal malignancy, or both from 2012 to 2018. RESULTS: In total, 135 (41.03%) SOTRs were diagnosed with IM without a preceding diagnosis of NMSC while only 42 (12.76%) patients diagnosed with IM had a preceding diagnosis of NMSC. SOTRs with a diagnosis of NMSC showed a significantly decreased risk of developing subsequent IM (hazard ratio [HR] 0.64, 95% confidence interval [95%CI] 0.44-0.94, P = 0.02) compared to those without a prior NMSC diagnosis. Liver and lung transplant patients showed a significantly decreased risk of developing subsequent IM after a diagnosis of NMSC (HR 0.09 and 0.43, respectively). When stratified by type of IM, only patients who were diagnosed with a hematological malignancy had a significantly lower risk of developing this malignancy if they had a prior NMSC (HR 0.26). CONCLUSIONS: The findings of this study suggest a protective effect of NMSC on subsequent IM in the organ transplant population.

Hidradenitis suppurativa and atopic dermatitis: A 2-way association.

BACKGROUND: The coexistence of hidradenitis suppurativa (HS) and atopic dermatitis (AD) had been reported but, to our knowledge, was not investigated in controlled studies. OBJECTIVE: To evaluate the bidirectional association between HS and AD. METHODS: A population-based retrospective cohort study was conducted to compare the incidence rate of AD among patients with HS (n = 6779) and age-, sex-, and ethnicity-matched control individuals (n = 33,260). Adjusted hazard ratios (HRs) and adjusted odds ratios were estimated. RESULTS: The incidence of AD was 2.51 (95% confidence interval [CI], 2.07-3.02) and 1.24 (95% CI, 1.10-1.40) per 1000 person-years among patients with HS and control individuals, respectively. Patients with HS were twice as likely to develop AD as control individuals (HR, 2.06; 95% CI, 1.64-2.58). Furthermore, the prevalence of pre-existing AD was higher in patients with HS than in control individuals (2.5% vs 1.8%, respectively; P < .001). A history of AD was associated with a 40% increase in the odds of HS (odds ratio, 1.41; 95% CI, 1.19-1.67). Relative to patients with isolated HS, those with a dual diagnosis of HS and AD were younger and had a female predominance, lower prevalence of smoking, and lower body mass index. LIMITATIONS: Retrospective data collection. CONCLUSIONS: A bidirectional association between HS and AD was observed. Dermatologists should be aware of this association.

The trichoscopic features of hair shaft anomalies induced by epidermal growth factor receptor inhibitors: A case series.

BACKGROUND: Although the clinical hair changes that occur under treatment with epidermal growth factor receptor inhibitors (EGFRIs) are documented, their trichoscopic features have not been reported. OBJECTIVE: To evaluate the trichoscopic findings in scalp and facial hair, induced by EGFRI treatment. METHODS: Patients treated with EGFRIs at a tertiary oncodermatology clinic in 2015 through 2017 were evaluated for macroscopic and trichoscopic changes. RESULTS: The cohort included 23 patients (13 women; median age, 68 years) treated with EGFRIs for an average of 13 months (range, 2-40 months). Macroscopically, 18 patients (78%) had dry, lusterless, coarse, kinky, brittle scalp hair, and 17 (74%) had trichomegaly of the eyebrows/eyelashes. Trichoscopic findings were of hair shaft anomalies including pili torti, affecting scalp hair in 20 patients (87%), eyebrows in 6 (26%), and eyelashes in 8 (50%), and asymmetric hyperpigmented fusiform widening of hair scalp in 3 (13%), eyebrows in 10 (43%), and eyelashes in 4 (25%). Dermoscopic findings of the peri- and interfollicular skin were scale, whitish erythematous structureless areas, and branching vessels. LIMITATIONS: Lack of trichoscopic-histologic correlation, lack of baseline examination. CONCLUSION: The trichoscopic correlates of the macroscopic hair changes under EFGRI treatment include pili torti, and asymmetric hyperpigmented fusiform widening, with dermoscopic cutaneous manifestations of scale, whitish erythematous structureless areas, and branching vessels.