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Competing Interests: Conflicts of interest CL declares consulting and advisory fees from BMS, MSD, Pierre Fabre and Sanofi. SM declares consulting and advisory fees from Novartis and Roche, and research funding from Biocartis. The other authors declare no conflicts of interest.

Competing Interests: Conflicts of interests M.B. declares receipt of consulting fees from Innate Pharma, Takeda, Kyowa Kirin, BMS, Recordati Rare Diseases and Sanofi.

Background and Hypothesis: Polypharmacy is a significant clinical issue for patients on dialysis but has been incompletely studied. We investigated the prevalence and costs of polypharmacy in a population-based cohort of participants treated with hemodialysis (HD) or peritoneal dialysis (PD)., Methods: We studied adults aged ≥ 20 years in Alberta, Canada receiving maintenance HD or PD as of March 31, 2019. We characterized participants as users of 0-29 drug categories of interest and those aged ≥ 65 as users/non-users of potentially inappropriate medications (PIM). We calculated the number of drug categories, daily pill burden, total annual cost, and annual cost per participant, and compared this to an age- and sex-matched cohort from the general Alberta population., Results: Among 2 248 participants (mean age 63 years; 39% female) on HD (n = 1 781) or PD (n = 467), the median number of prescribed drug categories was 6 [interquartile range (IQR) 4, 8]; median daily pill burden was 8.0 (IQR 4.6, 12.6) pills/day, with 5% prescribed ≥ 21.7 pills/day, and 16.5% prescribed ≥ 15 pills/day. Twelve % were prescribed at least one drug that is contraindicated in kidney failure. The median annual per participant cost was ${\$}$3,831, totaling approximately ${\$}$11.6 million annually for all participants. When restricting to the 1 063 participants aged ≥ 65, the median number of PIM categories was 2 (IQR 1, 2), with a median PIM pill burden of 1.2 pills/day (IQR 0.5, 2.4). Compared to PD participants, HD participants had similar daily pill burden, higher use of PIM, and higher annual per participant cost. Pill burden and associated costs for participants on dialysis were more than 3-fold and 10-fold higher, respectively, compared to the matched participants from the general population., Conclusion: Participants on dialysis have markedly higher use of prescription medications and associated costs than the general population. Effective methods to de-prescribe in the dialysis population are needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Kimura disease (KD) is a rare, chronic angiolymphoproliferative inflammatory disease appearing to be mostly restricted to the skin and soft tissue. Cutaneous involvement of KD includes head and/or neck nodules showing suggestive histological features, frequently associated with an atopic dermatitis-like or prurigo-like presentation. KD is challenging to treat, with high rate of recurrence using current therapeutic strategies. Evidence for involvement of a T-helper type 2 (Th2) immune response in KD pathogenesis has been found in previous studies. Consequently, this study aimed to determine the efficacy and safety of dupilumab, a human monoclonal antibody that inhibits signalling of key Th2 cytokines, interleukin (IL)-4 and IL-13, within a single-centre cohort of patients with cutaneous KD. Two adults with a diagnosis of refractory (failure of at least one treatment line) cutaneous-restricted KD based on clinical, biological, histological, molecular and imaging findings received dupilumab for KD, and showed dramatic response with a good safety profile., Competing Interests: Conflicts of interest G.B. has consulted for Novartis (board). M.J. is an investigator and medical/scientific advisor for Sanofi. A.P. has received honoraria from Sanofi as a speaker. M.B. has received grants/research support from Kyowa kirin and Takeda; and has received honororia or consultation fees from Bristol Myers Squibb, Cerba Research, Innate Pharma, Kyowa kirin, L’Oréal, Takeda and Sanofi. J.D.B. is an investigator and medical/scientific advisor for Sanofi. T.M. has consulted for Janssen, Novartis and Sanofi (boards). The remaining authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Primary cutaneous peripheral T-cell lymphomas with a T-follicular helper phenotype (pcTFH-PTCL) are poorly characterized, and often compared to, but not corresponding with, mycosis fungoides (MF), Sézary syndrome, primary cutaneous CD4 + lymphoproliferative disorder, and skin manifestations of angioimmunoblastic T-cell lymphomas (AITL)., Objectives: We describe the clinicopathological features of pcTFH-PTCL in this original series of 23 patients, and also characterize these cases molecularly., Methods: Clinical and histopathological data of the selected patients were reviewed. Patient biopsy samples were also analysed by targeted next-generation sequencing., Results: All patients (15 men, eight women; median age 66 years) presented with skin lesions, without systemic disease. Most were stage T3b, with nodular (n = 16), papular (n = 6) or plaque (atypical for MF, n = 1) lesions. Three (13%) developed systemic disease and died of lymphoma. Nine (39%) patients received more than one line of chemotherapy. Histologically, the lymphomas were CD4 + T-cell proliferations, usually dense and located in the deep dermis (n = 14, 61%), with the expression of at least two TFH markers (CD10, CXCL13, PD1, ICOS, BCL6), including three markers in 16 cases (70%). They were associated with a variable proportion of B cells. Eight patients were diagnosed with an associated B-cell lymphoproliferative disorder (LPD) on biopsy, including Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (n = 3), EBV + LPD (n = 1) and monotypic plasma cell LPD (n = 4). Targeted sequencing showed four patients to have a mutated TET2-RHOAG17V association (as frequently seen in AITL) and another a TET2/DNMT3A/PLCG1/SETD2 mutational profile. The latter patient, one with a TET2-RHOA association, and one with no detected mutations, developed systemic disease and died. Five other patients showed isolated mutations in TET2 (n = 1), PLCG1 (n = 2), SETD2 (n = 1) or STAT5B (n = 1)., Conclusions: Patients with pcTFH-PTCL have pathological and genetic features that overlap with those of systemic lymphoma of TFH derivation. Clinically, most remained confined to the skin, with only three patients showing systemic spread and death. Whether pcTFH-PTCL should be integrated as a new subgroup of TFH lymphomas in future classifications is still a matter of debate. What is already known about this topic? There is a group of cutaneous lymphomas that express T-follicular helper (TFH) markers that do not appear to correspond to existing World Health Organization diagnostic entities. These include mycosis fungoides, Sézary syndrome, or primary cutaneous CD4 + small/medium-sized T-cell lymphoproliferative disorder or cutaneous extensions of systemic peripheral T-cell lymphomas (PTCL) with TFH phenotype. What does this study add? This is the first large original series of patients with a diagnosis of primary cutaneous PTCL with a TFH phenotype (pcTFH-PTCL) to be molecularly characterized. pcTFH-PTCL may be a standalone group of cutaneous lymphomas with clinicopathological and molecular characteristics that overlap with those of systemic TFH lymphomas, such as angioimmunoblastic T-cell lymphoma, and does not belong to known diagnostic groups of cutaneous lymphoma. This has an impact on the treatment and follow-up of patients; the clinical behaviour needs to be better clarified in further studies to tailor patient management., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Mogamulizumab, an anti-CCR4 monoclonal antibody, has been shown to increase progression-free survival in cutaneous T-cell lymphoma., Objectives: We hypothesized that besides the targeted depletion of Sézary cells (SCs), mogamulizumab may reshape the immune tumour microenvironment., Methods: Both malignant and benign compartments from 26 patients with B2 stage Sézary syndrome before mogamulizumab initiation were prospectively analysed using KIR3DL2 and TCRVβ markers, serological markers and molecular assessments of clonality., Results: Prior to mogamulizumab, the benign subset of CD4 + T cells displayed exhausted phenotypes, with an increased gradient in programmed death-1, TIGIT, DNAM-1, CD27, CD28 and CD70 expression from age-matched controls to patients' benign CD4 + T cells and to SCs. All patients presented SCs with heterogeneous phenotypes, and differential expression of individual markers was found within distinct malignant subsets. Early complete blood response was observed in 17 of 26 patients and was associated with higher baseline CCR4 expression. A drastic decrease in benign T cells and activated regulatory T-cell counts was observed during the first 4 weeks. Long-term follow-up revealed the emergence of an immune restoration involving CD8 + and naive and stem memory CD4 + T cells, with almost complete disappearance of exhausted lymphocytes. Development of resistance or tumour escape to mogamulizumab was associated with the emergence of CCR4 - SCs in blood and skin, displaying significant changes in their heterogeneity patterns, and not explained only by mutations within CCR4 coding regions., Conclusions: Mogamulizumab likely contributes to the restoration of efficient immunity and reshapes not only the malignant lymphocyte subset but also the benign subset. These results have potential implications for optimal therapeutic sequences and/or combinations. What is already known about this topic? Management of Sézary syndrome (SS) involves successive therapies that participate as cause and consequence in the emergence of resistant clones, on a background of immunodeficiency. We and others have reported the complex and dynamic heterogeneity of Sézary cells (SCs) during disease progression. Mogamulizumab therapy, by targeting the skin-homing receptor CCR4, mainly expressed by SCs, has been shown to increase progression-free survival in patients with SS. What does this study add? Using multicolour flow cytometry, we provide quantification of CCR4 and immune checkpoint molecules on malignant SCs and benign CD4 + T cells from patients with SS, separated using KIR3DL2 and TCRVβ expression. Mogamulizumab is not only aimed at eradicating malignant SCs but potentially contributes to the restoration of efficient immunity. Tumour escape is associated with the emergence of CCR4 - SCs, not explained only by mutations within CCR4 coding regions., (© 2022 British Association of Dermatologists.)

Background: The differential diagnosis of atypical dermal nonepidermotropic CD8 + lymphocytic infiltrates includes a heterogeneous spectrum of lymphoproliferations with overlapping histological and phenotypic features, but divergent clinical manifestations and prognoses. As these neoplasms are rare, more data on their clinicopathological presentation and course are needed., Objectives: To assess the clinical, histological and immunophenotypic features; outcomes of; and differences between dermal CD8 + lymphoproliferations., Methods: Retrospective analysis of a series of 46 patients and biopsies by the international EORTC Cutaneous Lymphoma Group., Results: The dermal CD8 + lymphoproliferations (n = 46) could be assigned to one of three groups: (i) cutaneous acral CD8 + T-cell lymphoma (n = 31), characterized mostly by a solitary nodule arising at acral sites, a monotonous dermal infiltrate of small-to-medium-sized CD8 + lymphocytes with a characteristic dot-like pattern of CD68, a low proliferation rate and an excellent prognosis; (ii) primary cutaneous CD8 + peripheral T-cell lymphoma, unspecified/NOS (n = 11), presenting with one or multiple rapidly evolving tumours, mostly medium-sized pleomorphic CD8 + tumour cells with expression of several cytotoxic markers, and high proliferative activity; and (iii) cutaneous CD8 + lymphoproliferations (n = 4), associated with congenital immunodeficiency syndromes in two patients with persisting localized or disseminated violaceous to brownish plaques on the extremities, a histiocyte-rich infiltrate of mostly small CD8 + lymphocytes with subtle atypia and a protracted course; and papular CD8 + eruptions in two patients with acquired immunosuppression., Conclusions: A constellation of distinct clinical, histopathological and phenotypic features allows discrimination and assignment of dermal CD8 + infiltrates into distinct disease entities. Primary cutaneous acral CD8 + lymphoma, assigned a provisional category in current lymphoma classifications, is a distinct and reproducible entity. A correct diagnosis is essential to avoid unnecessarily aggressive treatment for indolent CD8 + lymphoproliferations and to identify cases with underlying immuno-deficiency or potential for dismal outcome., (© 2022 British Association of Dermatologists.)

Background: The outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear., Objectives: To study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus., Methods: This observational study was conducted during 9-16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included., Results: Histological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic-natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL., Conclusions: Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations., (© 2021 British Association of Dermatologists.)

Background: Lymphomatoid papulosis (LyP) type D (LyP D) and type E (LyP E) have recently been described in small series of cases or isolated case reports., Aim: To further describe the clinical and histological features of LyP D and E based on a retrospective multicentre study., Methods: The clinical and histopathological features of 29 patients with an initial diagnosis of LyP D or LyP E were retrospectively assessed using standardized forms., Results: After exclusion of 5 cases, 24 patients (14 LyP D, 10 LyP E) were enrolled in the study. The median follow-up was 2.5 years (range 1 month to 13 years). LyP D was characterized by multiple recurrent self-regressing small papules that developed central erosion or necrosis, whereas LyP E presented as papulonodular lesions that rapidly evolved into necrotic eschar-like lesions > 10 mm in size. Epidermal changes were more frequent in LyP D, whereas dermal infiltrates were deeper in LyP E. Anaplastic cytology was rare and the DUSP22 rearrangement was never observed. Two patients (8%) had an associated cutaneous lymphoma., Conclusion: LyP D and E have distinct clinical findings and may be associated with other cutaneous lymphomas., (© 2021 British Association of Dermatologists.)

Background: The prognosis of Sézary syndrome (SS) and mycosis fungoides (MF) depends on lymph node (LN) involvement. The usefulness of LN image-guided core-needle biopsies (CNBs), instead of surgical sampling, has been poorly evaluated., Objectives: To determine the prognostic value of LN CNB in MF/SS., Methods: A retrospective search was conducted to identify all LN biopsy specimens of MF/SS between 2008 and 2019. Biopsies were staged according to the International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer (ISCL/EORTC) criteria. We performed immunolabelling and determined the tumour clone frequency (TCF) by high-throughput sequencing of the T-cell receptor beta locus., Results: We included 119 consecutive biopsies from 100 patients, 45 with MF and 55 with SS. N1, N2 and N3 stages were diagnosed in 34 (29%), 26 (22%) and 59 (49%) cases, respectively. The TCF, Ki67 index, and percentage of cells positive for thymocyte selection-associated high mobility group box protein (TOX), programmed cell death protein 1 (PD1), killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2) and cluster of differentiation (CD)30 were all positively correlated with the N stage. Median overall survival (OS) for N1/N2 vs. N3 patients was 42 months (range 26-not reached) vs. 14 months (range 5-30), respectively (P < 0·001). In univariate analyses, an age > 75 years, LN short-axis diameter > 15 mm, N3 stage, presence of large-cell transformation, TOX > 60%, PD1 > 25%, Ki67 > 30%, KIR3DL2 > 15%, CD30 > 10% and TCF > 25% were identified as adverse prognostic factors. In multivariate analyses, only an age > 75 years and Ki67 index > 30% were associated with reduced OS. We developed a new prognostic index associating the N stage and the Ki67 index, which better discriminates N3 patients with poor prognosis., Conclusions: CNB allows an objective assessment of the LN involvement in MF/SS, relevant for staging and prognosis., (© 2021 British Association of Dermatologists.)

Background: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time., Objectives: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients., Methods: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included., Results: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time., Conclusions: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases., (© 2020 British Association of Dermatologists.)

Background: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF)., Objectives: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures., Methods: In total, 395 newly diagnosed patients with early-stage MF (stage IA-IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review., Results: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA-IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease., Conclusions: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues., (© 2020 British Association of Dermatologists.)

Objectives: Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are important for antibacterial immunity and may have regulatory roles. MAIT cells are decreased during SLE. However, their frequencies and phenotype have not been investigated in DM. We studied MAIT cell frequencies and phenotype in DM patients with active and inactive disease (after treatment)., Methods: Peripheral blood flow cytometry analysis of MAIT cells was compared between DM (n = 22), SLE (n = 10), psoriasis (n = 7) and atopic dermatitis (n = 5) patients, and healthy controls (n = 19)., Results: A dramatic decrease of circulating MAIT cell frequency was observed in active DM and SLE patients compared with healthy controls and other inflammatory skin diseases [active DM: median = 0.25% (interquartile range 0.19-0.6%), P < 0.0001; active SLE: median = 0.61 (0.55-0.77), P < 0.0001 vs healthy controls: 2.32% (1.18-4.45%)]. MAIT cells from active DM patients had an abnormal phenotype including increased expression of CD25 and cytotoxic T-lymphocyte-associated protein 4 that correlated with their low frequency in the blood., Conclusion: In DM, peripheral blood MAIT cells are dramatically reduced and have an activated/exhausted phenotype that may be linked to increased activation-induced cell death., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Psoriasiform chronic graft-versus-host disease (GvHD) is a rare clinical presentation recently described after allogeneic haematopoietic stem cell transplantation. It is characterized by the combination of clinical and pathological characteristics of psoriasis together with pathological features of chronic GvHD. As described for psoriasis, psoriasiform chronic GvHD is characterized by the infiltration of T helper 17 CD8 + T cells producing both interferon-γ and interleukin-17. However, no data are available about the efficacy of interleukin-17 blockade in the treatment of patients with psoriasiform chronic GvHD. What's already known about this topic? Psoriasiform chronic graft-versus-host disease (GvHD) is a rare clinical presentation with a poor durable response to steroids. Animal models and human data suggest that psoriasiform GvHD could be induced through interleukin-17 production by donor T cells. What does this study add? We describe the first case of a patient with psoriasiform GvHD and persistent improvement on treatment with secukinumab, an anti-interleukin-17A antibody., (© 2019 British Association of Dermatologists.)

Immune checkpoint inhibitors are now the standard of care in the treatment of several types of cancer. Cutaneous immune-related adverse events (irAEs) are usually of low grade and reversible, while endocrine irAEs are generally irreversible and managed with hormone replacement therapy. We report a 47-year-old patient, treated with the anti-programmed cell death (PD)1 antibody pembrolizumab for a metastatic melanoma, who developed severe lipodystrophy after 10 months of treatment, characterized by the loss of subcutaneous fat tissue, central obesity and insulin resistance with a decreased leptin level. Histological analysis of a cutaneous biopsy revealed subcutaneous fat cell destruction associated with oedema, the presence of lipophages, and a CD3 + lymphocytic infiltrate involving the panniculus. This led to the diagnosis of anti-PD-1-induced acquired generalized lipodystrophy, after ruling out differential diagnoses (i.e. genetic and systemic autoimmune diseases). No corticosteroids were introduced considering the high risk of inducing severe metabolic complications, and pembrolizumab was discontinued as complete response of the melanoma was achieved. However, after 12 months of follow-up, lipodystrophy and its severe metabolic complications are still ongoing. What's already known about this topic? Anti-programmed cell death (PD)1 agents are now a standard of care in the treatment of several cancers, including melanoma. Endocrine and cutaneous immune-related adverse events (irAEs) are among the most frequent irAEs (14-30% and 30-40%, respectively) in patients treated with immune checkpoint inhibitors. What does this study add? Acquired generalized lipodystrophy can occur during anti-PD1 therapy and is associated with severe metabolic complications. With the increase in anti-PD1 prescription in several cancer types, clinicians must be aware of the whole range of irAEs that may occur., (© 2019 British Association of Dermatologists.)

Background: Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web-based data collection system for early-stage MF with legal data-sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in-built intelligence in the database system ensures accurate staging., Objectives: To develop a prognostic index for MF., Methods: Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies., Results: In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early-stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 12-90)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF., Conclusions: This confirmed early-stage MF cohort is being followed-up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex., (© 2018 British Association of Dermatologists.)

The erythrodermic ulcerated form of mycosis fungoides (MF) is exceptional, and treatment of refractory cases is challenging. Brentuximab vedotin (BV) is a monoclonal antibody combined with monomethyl auristatin E, recently approved for the treatment of refractory CD30 + cutaneous T-cell lymphoma. We report a case of refractory MF in a 56-year-old man with a long history of large-plaque parapsoriasis, as revealed by psoriasiform erythroderma, treated initially with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) polychemotherapy, inducing a 2-year complete response. After relapse, interferon and gemcitabine were unsuccessful. Finally, treatment with BV was decided upon, despite the absence of CD30 expression. After three infusions of BV 1·8 mg kg -1 , we achieved a complete and stable response, allowing an allogeneic stem cell transplant. The patient is still in complete remission, 19 months after the graft. This case illustrates the possibility of using BV in refractory CD30 - MF as a salvage therapy., (© 2018 British Association of Dermatologists.)

Background: There is a lack of clear benefit and a potential risk of bleeding with direct oral anticoagulant (DOAC) use in chronic kidney disease (CKD) and dialysis patients with atrial fibrillation. The objective of this study was to evaluate how treatment with DOACs affects stroke and bleeding outcomes compared with warfarin or aspirin., Methods: We conducted a systematic review of randomized controlled trials, cohort studies and case series, and searched electronic databases from 1946 to 2017. Studies evaluating stroke and bleeding outcomes with DOAC use in CKD and dialysis patients were included., Results: From 8008 studies, 10 met the inclusion criteria. For moderate CKD patients (estimated glomerular filtration rate  <60 mL/min/1.73 m2), there was no difference in stroke outcomes between dabigatran 110 mg [hazard ratio (HR) 0.78, 95% confidence interval (95% CI) 0.51-1.21], rivaroxaban (HR 0.82-0.84, 95% CI 0.25-2.69) and edoxaban (HR 0.87, 95% CI 0.65-1.18) versus warfarin. Dabigatran (150 mg twice daily) and apixaban reduced risk of stroke or systemic embolism significantly more than warfarin for moderate CKD patients (HR 0.55, 95% CI 0.34-0.89 and HR 0.61, 95% CI 0.39-0.94, respectively). Edoxaban and apixaban were associated with reduced major bleeding events (HR 0.50-0.76) compared with warfarin. Rivaroxaban and dabigatran 110 mg and 150 mg showed no significant difference in major bleeding versus warfarin. In hemodialysis (HD) patients, there was no difference in stroke outcomes between apixaban, dabigatran [relative risk (RR) 1.71, 95% CI 0.97-2.99] or rivaroxaban (RR 1.8, 95% CI 0.89-3.64) versus warfarin. In HD patients, rivaroxaban and dabigatran were associated with an increased major bleeding risk (RR 1.45-1.76), whereas there was no major bleeding difference with apixaban compared to warfarin., Limitations: The heterogeneity of major bleeding and stroke definitions of the 10 included studies., Conclusions: Clinicians should continue to weigh the risk of stroke versus bleeding before prescribing DOACs in the CKD and dialysis population.

Orf is a DNA parapoxvirus transmitted to humans by contact with infected goats and sheep. Many complications have been reported after orf infection, including erythema multiforme. A few cases of autoimmune bullous dermatosis complicating orf disease have been reported to date. They are usually characterized by tense blister eruptions with or without mucosal involvement; linear deposition of C3, IgG and/or IgA along the basement membrane; and negativity of indirect immunofluorescence analysis and enzyme-linked immunosorbent assay (ELISA) (performed in four of 11 reported cases). These analyses have targeted antigens of bullous pemphigoid, mucous membrane pemphigoid or epidermolysis bullosa acquisita, except one case of mucosal pemphigoid with antilaminin-332 antibodies. We describe the case of a patient who presented with an ulceration on his finger 10 days after direct contact with a lamb during Eid al-Adha. Four weeks later he developed a severe tense blistering eruption associated with mucous membrane erosions. Indirect immunofluorescence analysis using the patient's serum revealed circulating antibasement membrane IgG that bound the dermal side of salt-split skin. ELISA was positive for recombinant immunodominant NC1 domain of type VII collagen. We finally diagnosed epidermolysis bullosa acquisita complicating probable human orf infection., (© 2017 British Association of Dermatologists.)

Background: KIR3DL2, an inhibitory receptor expressed by natural killer cells and a subset of normal CD8(+) T cells, is aberrantly expressed in neoplastic cells in transformed mycosis fungoides and Sézary syndrome. Anti-KIR3DL2 targeted antibody therapy has shown potent activity in preclinical models for these diseases., Objectives: To examine the expression of KIR3DL2 and its potential use as a therapeutic target in patients with primary cutaneous anaplastic large-cell lymphoma (pcALCL), the most aggressive cutaneous CD30(+) lymphoproliferative disease., Methods: Samples from 11 patients with pcALCL and three CD30(+) lymphoproliferative disease cell lines - Mac1, Mac2a and Mac2b - were used in KIR3DL2 expression studies using immunohistochemistry, flow cytometry and reverse-transcriptase quantitative polymerase chain reaction. The effect of IPH4102, a monoclonal humanized IgG1 targeting KIR3DL2, was assessed by in vitro cytotoxicity assays against Mac1, Mac2a and Mac2b using allogeneic peripheral blood mononuclear cells as effectors., Results: KIR3DL2 mRNA and protein were found in all human samples of pcALCL, and in the Mac2a and Mac2b cell lines. KIR3DL2 protein expression was present on 85·8 ± 14·0% of CD30(+) skin-infiltrating tumour cells. In vitro functional studies showed that KIR3DL2(+) Mac2a and Mac2b pcALCL lines are sensitive to antibody-derived cytotoxicity mediated by IPH4102, through activation of natural killer cells, in a concentration-dependent manner., Conclusions: pcALCL tumour cells express KIR3DL2, and we provide preclinical proof of concept for the use of IPH4102, a humanized anti-KIR3DL2 antibody, to treat patients with primary cutaneous CD30(+) ALCL., (© 2016 British Association of Dermatologists.)

Background: Patients with erythrodermic disease are a diagnostic challenge regarding the clinical and histological differential diagnosis., Objectives: To evaluate histopathological and immunohistochemical diagnostic markers for Sézary syndrome., Methods: Ninety-seven erythrodermic cases [Sézary syndrome (SS), n = 57; erythrodermic inflammatory dermatoses (EIDs), n = 40] were collected by the EORTC Cutaneous Lymphoma Task Force histopathology group. Evaluation criteria were (i) epidermal and dermal changes; (ii) morphology of the infiltrate; (iii) immunohistochemical analysis of marker loss (CD2, CD3, CD4, CD5 and CD7); (iv) bystander infiltrate by staining for CD8, FOXP3 and CD25; and (v) expression of Ki-67, CD30, PD-1 and MUM-1., Results: The workshop panel made a correct diagnosis of SS in 51% of cases (cutaneous T-cell lymphoma 81%) and of EID in 80% without clinical or laboratory data. Histology revealed a significantly increased degree of epidermotropism (P < 0.001) and more intraepidermal atypical lymphocytes (P = 0.0014) in SS biopsies compared with EID. Pautrier microabscesses were seen only in SS (23%) and not in EID (P = 0.0012). SS showed significantly more dermal cerebriform and blastic lymphocytes than EID. Immunohistochemistry revealed a significant loss of CD7 expression (< 50%) in 33 of 51 (65%) cases of SS compared with two of 35 (6%) EID (P < 0.001). The lymphocytic infiltrate in SS skin samples was found significantly to express PD-1 (P = 0.0053), MUM-1 (P = 0.0017) and Ki-67 (P < 0.001), and showed less infiltration of CD8(+) lymphocytes (P < 0.001). A multivariate analysis identified CD7 loss, increased numbers of small cerebriform lymphocytes, low numbers of CD8(+) lymphocytes and increased proliferation (Ki-67(+) lymphocytes) as the strongest indicators for the diagnosis of SS., Conclusions: A number of different histological and immunophenotypical criteria are required to differentiate between SS and EIDs., (© 2015 British Association of Dermatologists.)

Background: Patients undergoing hemodialysis frequently report pain with multifactorial causes, not limited to that experienced directly from hemodialysis treatment. Their pain may be nociceptive, neuropathic, somatic or visceral in nature. Despite this, pain in this population remains under-recognized and under-treated. Although several tools have been used to measure pain in patients undergoing hemodialysis as reported in the literature, none of them have been validated specifically in this population. The objective for this review was to compare and contrast these pain assessment tools and discuss their clinical utility in this patient population., Methods: To identify pain assessment tools studied in patients undergoing hemodialysis, a literature search was performed in PubMed and Medline. An expert panel of dialysis and pain clinicians reviewed each tool. Each pain assessment tool was assessed on how it is administered and scored, its psychometric properties such as reliability, validity and responsiveness to change, and its clinical utility in a hemodialysis population. Brief Pain Inventory, McGill Pain Questionnaire, Pain Management Index, Edmonton Symptom Assessment System, Visual Analogue Scale and Faces Pain Scale were evaluated and compared., Results: This assessment will help clinicians practicing in nephrology to determine which of these pain assessment tools is best suited for use in their individual clinical practice.