Clinicopathological features, MCPyV status and outcomes of Merkel cell carcinoma in solid-organ transplant recipients: a retrospective, multicentre cohort study.

BACKGROUND: The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. OBJECTIVE: To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. METHODS: Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. RESULTS: A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. LIMITATIONS: Retrospective design and heterogeneity of SOTR cohort. CONCLUSIONS: MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.

A case of lupus-like syndrome in a patient receiving adalimumab and a brief review of the literature on drug-induced lupus erythematosus.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced lupus erythematosus occurs with some drugs and resolves with their withdrawal. Anti-TNF therapies have been found to be associated with a lupus-like syndrome, which is clinically distinct from classical drug-induced as well as idiopathic lupus erythematosus. CASE DESCRIPTION: We describe a case of a patient with severe psoriasis, who developed muscle pain with paraesthesia accompanied by ANA titres elevation with adalimumab treatment. The condition resolved after adalimumab cessation, and the patient was started on ustekinumab with good results. WHAT IS NEW AND CONCLUSION: Ustekinumab might be a useful treatment option for patients with a history of TNF-induced lupus-like syndrome.

Painful skin lesions and squamous cell carcinoma predict overall mortality risk in organ transplant recipients: a cohort study.

BACKGROUND: Organ transplant recipients (OTRs) have a highly increased risk of cutaneous squamous cell carcinomas (SCCs). Sensation of pain in cutaneous tumours is a powerful patient-reported warning signal for invasive SCCs in OTRs. OBJECTIVES: To investigate the impact of painful vs. painless skin lesions and SCC vs. other skin lesions on the overall mortality risk in OTRs. METHODS: We followed 410 OTRs from 10 different centres across Europe and North America between 2008 and 2015. These patients had been enrolled in an earlier study to define clinically meaningful patient-reported warning signals predicting the presence of SCC, and had been included if they had a lesion requiring histological diagnosis. Cumulative incidences of overall mortality were calculated using Kaplan-Meier survival analysis, and risk factors were analysed with Cox proportional hazard analysis. RESULTS: There was an increased overall mortality risk in OTRs who reported painful vs. painless skin lesions, with a hazard ratio (HR) of 1·6 [95% confidence interval (CI) 0·97-2·7], adjusted for age, sex and other relevant factors. There was also an increased overall mortality risk in OTRs diagnosed with SCC compared with other skin lesions, with an adjusted HR of 1·7 (95% CI 1·0-2·8). Mortality due to internal malignancies and systemic infections appeared to prevail in OTRs with SCC. CONCLUSIONS: We suggest that OTRs have an increased overall mortality risk if they develop painful skin lesions or are diagnosed with cutaneous SCC.

Effect of etanercept therapy on psoriasis symptoms in patients from Latin America, Central Europe, and Asia: a subset analysis of the PRISTINE trial.

BACKGROUND: Psoriasis prevalence and characteristics in Asia, Central Europe, and Latin America have not been thoroughly investigated and there are no large trials for biologic treatments for patients from these regions. The goal of this analysis was to report clinical response to anti-tumor necrosis factor-alpha treatment in these patients. METHODS: Patients from Argentina, Czech Republic, Hungary, Mexico, Taiwan, and Thailand (N=171) were included in this subset analysis of the PRISTINE trial. Patients with stable moderate-to-severe plaque psoriasis were blinded and randomized to receive etanercept 50 mg once weekly (QW) or biweekly (BIW) for 12 weeks, followed by 12 weeks of open-label QW treatment with etanercept 50 mg through week 24 (QW/QW vs. BIW/QW). Concomitant methotrexate (≤20 mg/week) and mild topical corticosteroids or other agents were permitted at the physician's discretion, in accordance with therapeutic practice. RESULTS: As early as week 8, 26.7 % in the etanercept QW group and 44.0 % in the BIW group achieved Psoriasis Area and Severity Index (PASI) 75. At weeks 12 and 24, respectively, PASI 75 increased to 39.5 % and 62.8 % in the QW/QW group and 66.7 % and 83.3 % in the BIW/QW group. PASI 75 was significantly different between treatment groups from week 8 through the end of study (p<0.05). The Kaplan-Meier estimate of the proportions achieving PASI 75 in QW/QW and BIW/QW groups, respectively, was 27.4 % and 45.8 % through week 8; 41.9 % and 68.7 % through week 12; and 72.5 % and 95.2 % through week 24. CONCLUSIONS: Treatment with etanercept 50 mg provided rapid relief of psoriasis symptoms in patients from Asia, Central Europe, and Latin America. A more rapid response was observed in patients who received BIW treatment for the first 12 weeks which was sustained after reducing to QW dosing for the subsequent 12 weeks. Response rates were similar to those observed in the overall PRISTINE population. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00663052 .

Pain identifies squamous cell carcinoma in organ transplant recipients: the SCOPE-ITSCC PAIN study.

Organ transplant recipients (OTR) are at high risk for cutaneous squamous cell carcinomas (SCC). We aimed to define clinically meaningful patient-reported warning signals predicting the presence of invasive SCC.Patient-reported signs and symptoms of 812 consecutively biopsied skin lesions from 410 OTR were determined by questionnaire and physical examination and related to the subsequent biopsy-proven diagnoses. Receiver-operating characteristic (ROC) curve analyses were used as a measure of distinction between the predictive values of patient-reported warning signals and the occurrence of SCC. Pain was an independent predictive patient-reported warning signal for a biopsy-proven invasive SCC. The odds ratio from the fully adjusted model predicting SCC was 4.4(95% confidence interval: 2.4­8.2). Higher scores on the visual analog scale (VAS) for pain were associated witha greater likelihood for the presence of SCC compared to none or mild pain. The for scores on the VAS from 1to 3, 4 to 6 and 7 to 10 were 4.9 (2.2­10.5), 2.3 (0.96­5.5)and 16.5 (3.6­75.8), respectively. Pain is the most powerful patient-reported warning signal for invasive cutaneous SCC in OTR. Empowerment of patients by education could accelerate diagnosis and treatment of cutaneous SCC.

Primary cutaneous posttransplant lymphoproliferative disorders in solid organ transplant recipients: a multicenter European case series.

Primary cutaneous posttransplant lymphoproliferative disorders (PTLD) are rare. This retrospective, multicenter study of 35 cases aimed to better describe this entity. Cases were (re)-classified according to the WHO-EORTC or the WHO 2008 classifications of lymphomas. Median interval between first transplantation and diagnosis was 85 months. Fifty-seven percent of patients had a kidney transplant. Twenty-four cases (68.6%) were classified as primary cutaneous T cell lymphoma (CTCL) and 11 (31.4%) as primary cutaneous B cell PTLD. Mycosis fungoides (MF) was the most common (50%) CTCL subtype. Ten (90.9%) cutaneous B cell PTLD cases were classified as EBV-associated B cell lymphoproliferations (including one plasmablastic lymphoma and one lymphomatoid granulomatosis) and one as diffuse large B cell lymphoma, other, that was EBV-negative. Sixteen (45.7%) patients died after a median follow-up of 19.5 months (11 [68.8%] with CTCL [6 of whom had CD30(+) lymphoproliferative disorders (LPD)] and 5 [31.2%] with cutaneous B cell PTLD. Median survival times for all patients, CTCL and cutaneous B cell PTLD subgroups were 93, 93, and 112 months, respectively. Survival rates for MF were higher than those for CD30(+) LPD. The spectrum of primary CTCL in organ transplant recipients (OTR) is similar to that in the general population. The prognosis of posttransplant primary cutaneous CD30(+) LPD is worse than posttransplant MF and than its counterpart in the immunocompetent population. EBV-associated cutaneous B cell LPD predominates in OTR.

High-dose cytosine arabinoside-induced cutaneous reactions.

BACKGROUND: High-dose cytosine arabinoside (HDAC) is being used increasingly to treat haematological malignancies. The therapy is associated with various non-haematological negative side-effects, frequently involving the skin. OBJECTIVE: Our aim was to evaluate the actual occurrence of adverse skin reactions to HDAC over the 10-year period from 1989 to 1999. METHODS: One hundred and seventy-two subjects, 118 with acute myelogenous leukaemia and 54 with acute lymphoblastic leukaemia, between 16 and 71 years of age were treated with 226 post-remission consolidation regimens with HDAC (54 subjects underwent two cycles of treatment). Treatment was combined with standard doses of other cytotoxic drugs. A prospective study of the skin changes was then performed. RESULTS: The overall incidence of cutaneous reactions was almost 53%, with rashes occurring in 72.7% and 40.6% of subjects who received total doses of 30 and 24 g/m2, respectively. In the group of subjects who received a second cycle of treatment not all of those who experienced exanthema after the first cycle (44.4%) experienced this reaction after the second cycle (only 33.3%). The most commonly observed reactions were morbilliform eruptions on the trunk and extremities and acral erythema, although severe reactions with swelling and generalized urticaria developed in some cases. CONCLUSIONS: HDAC-induced cutaneous reactions in 53% of subjects. The skin changes were found to be dose related and most cleared spontaneously without requiring treatment. A clinical grading of cutaneous toxicity has been proposed to allow better comparison of cutaneous adverse effects in different reports.

Successful treatment of severe Shulman's syndrome by allogeneic bone marrow transplantation.

We describe a patient with severe Shulman's syndrome (ShS) (eosinophilic fasciitis). This auto-immune disease involved not only the skin and muscles, but the bone marrow as well - thereby fulfilling the criteria of severe aplastic anemia. As the disease was steroid-resistant, the patient underwent allogeneic bone marrow transplantation (BMT). Remission of ShS was achieved. Eight months later chronic GVHD developed and relapse of ShS (probably induced by GVHD) occurred. He was successfully treated with corticosteroids and the disappearance of GVHD was followed by cessation of the symptoms of ShS. At present (34 months following BMT) he is doing well and displays no signs of ShS or GVHD. This case suggests that an aggressive immunoablative preparative regimen with subsequent allogeneic BMT can result in long-lasting clinical remission of a severe auto-immune disease.