Amy Musiek

Ipilimumab-associated Sweet syndrome in a patient with high-risk melanoma

right nipple. B, Nevoid hyperkeratosis of the nipple. Orthokeratotic hyperkeratosis, acanthosis, papillomatosis, and a sparse superficial perivascular lymphocytic infiltrate (Hematoxylin-eosin stain; original magnification:340). C andD, Syringocystadenoma papilliferum. Papillary foci in continuity with the surface squamous epithelium. These papilla had a bilayered epithelium of inner columnar cells showing decapitation secretion and outer flattened cells as well as a fibrovascular core containing abundant plasma cells. C and D, Hematoxylin-eosin stain; original magnifications: C, 340; D 3200. J AM ACAD DERMATOL VOLUME 70, NUMBER 4 Letters e85

First-in-human Phase 1 Clinical Study of the IL-15 Superagonist Complex ALT-803 to Treat Relapse after Transplantation

New therapies for patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) are needed. Interleukin 15 (IL-15) is a cytokine that stimulates CD8+ T-cell and natural killer (NK) cell antitumor responses, and we hypothesized this cytokine may augment antileukemia/antilymphoma immunity in vivo. To test this, we performed a first-in-human multicenter phase 1 trial of the IL-15 superagonist complex ALT-803 in patients who relapsed >60 days after allo-HCT. ALT-803 was administered to 33 patients via the IV or subcutaneous (SQ) routes once weekly for 4 doses (dose levels of 1, 3, 6, and 10 μg/kg). ALT-803 was well tolerated, and no dose-limiting toxicities or treatment-emergent graft-versus-host disease requiring systemic therapy was observed in this clinical setting. Adverse events following IV administration included constitutional symptoms temporally related to increased serum IL-6 and interferon-γ. To mitigate these effects, the SQ route was tested. SQ delivery resulted in self-limited injection site rashes infiltrated with lymphocytes without acute constitutional symptoms. Pharmacokinetic analysis revealed prolonged (>96 hour) serum concentrations following SQ, but not IV, injection. ALT-803 stimulated the activation, proliferation, and expansion of NK cells and CD8+ T cells without increasing regulatory T cells. Responses were observed in 19% of evaluable patients, including 1 complete remission lasting 7 months. Thus, ALT-803 is a safe, well-tolerated agent that significantly increased NK and CD8+ T cell numbers and function. This immunostimulatory IL-15 superagonist warrants further investigation to augment antitumor immunity alone and combined with other immunotherapies. This trial was registered at www.clinicaltrials.gov as #NCT01885897.

Ponatinib-induced neutrophilic panniculitis

Ponatinib is a bcr‐abl tyrosine‐kinase inhibitor (TKI) used to treat resistant and refractory chronic myeloid leukemia and Philadelphia chromosome‐positive acute lymphoblastic leukemia that express bcr‐abl. Neutrophilic panniculitis has been described in rare cases of patients on other TKIs in the same class as ponatinib. We present the first case of neutrophilic panniculitis following treatment with ponatinib and summarize the other cases of panniculitis caused by TKIs.

Methotrexate-induced cutaneous ulceration in 3 nonpsoriatic patients: Report of a rare side effect

H&E: hematoxylin-eosin stain MTX: methotrexate RA: rheumatoid arthritis INTRODUCTION Methotrexate (MTX) is a commonly prescribed medication in the treatment of autoimmune conditions such as rheumatoid arthritis (RA) and psoriasis. MTX is a folic acid analog and DNA synthesis inhibitor that competitively inhibits dihydrofolate reductase. Well-known side effects of MTX include diarrhea, nausea/vomiting, anorexia, stomatitis, fatigue, and malaise. Cutaneous ulceration is a less commonly described sign of MTX toxicity in patients with psoriasis. Reported risk factors include relatively high MTX dosage, renal impairment, concurrent nonsteroidal anti-inflammatory drugs, age older than 55, folate deficiency, low serum albumin, and drug interactions. MTX-induced cutaneous ulceration in nonpsoriatic patients is rare, with the first case reported in 1998. Since 2011, only 5 cases have been reported. In this case series, we report MTX-induced cutaneous ulceration in 3 nonpsoriatic patients.

Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial

BACKGROUND Cutaneous T-cell lymphomas are rare non-Hodgkin lymphomas with substantial morbidity and mortality in advanced disease stages. We compared the efficacy of mogamulizumab, a novel monoclonal antibody directed against C-C chemokine receptor 4, with vorinostat in patients with previously treated cutaneous T-cell lymphoma. METHODS In this open-label, international, phase 3, randomised controlled trial, we recruited patients with relapsed or refractory mycosis fungoides or Sézary syndrome at 61 medical centres in the USA, Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the UK, Japan, and Australia. Eligible patients were aged at least 18 years (in Japan, ≥20 years), had failed (for progression or toxicity as assessed by the principal investigator) at least one previous systemic therapy, and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate haematological, hepatic, and renal function. Patients were randomly assigned (1:1) using an interactive voice web response system to mogamulizumab (1·0 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or vorinostat (400 mg daily). Stratification was by cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB-II vs III-IV). Since this study was open label, patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival by investigator assessment in the intention-to-treat population. Patients who received one or more doses of study drug were included in the safety analyses. This study is ongoing, and enrolment is complete. This trial was registered with ClinicalTrials.gov, number NCT01728805. FINDINGS Between Dec 12, 2012, and Jan 29, 2016, 372 eligible patients were randomly assigned to receive mogamulizumab (n=186) or vorinostat (n=186), comprising the intention-to-treat population. Two patients randomly assigned to mogamulizumab withdrew consent before receiving study treatment; thus, 370 patients were included in the safety population. Mogamulizumab therapy resulted in superior investigator-assessed progression-free survival compared with vorinostat therapy (median 7·7 months [95% CI 5·7-10·3] in the mogamulizumab group vs 3·1 months [2·9-4·1] in the vorinostat group; hazard ratio 0·53, 95% CI 0·41-0·69; stratified log-rank p<0·0001). Grade 3-4 adverse events of any cause were reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group. The most common serious adverse events of any cause were pyrexia in eight (4%) patients and cellulitis in five (3%) patients in the mogamulizumab group; and cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the vorinostat group. Two (67%) of three on-treatment deaths with mogamulizumab (due to sepsis and polymyositis) and three (33%) of nine on-treatment deaths with vorinostat (two due to pulmonary embolism and one due to bronchopneumonia) were considered treatment-related. INTERPRETATION Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma. FUNDING Kyowa Kirin.

Acute graft-versus-host disease following lung transplantation in a patient with a novel TERT mutation

Familial pulmonary fibrosis is associated with loss-of-function mutations in telomerase reverse transcriptase (TERT) and short telomeres. Interstitial lung diseases have become the leading indication for lung transplantation in the USA, and recent data indicate that pathogenic mutations in telomerase may cause unfavourable outcomes following lung transplantation. Although a rare occurrence, solid organ transplant recipients who develop acute graft-versus-host disease (GVHD) have very poor survival. This case report describes the detection of a novel mutation in TERT in a patient who had lung transplantation for familial pulmonary fibrosis and died from complications of acute GVHD.

Sustained remission of recalcitrant cutaneous lymphoid hyperplasia after thalidomide treatment

CASE REPORT A 66-year-old white man with a history of ulcerative colitis in remission for 5 years after infliximab treatment presented complaining of a pruritic and painful red rash over his face for greater than a year. Examination found erythematous edematous granulomatous papules and plaques (Fig 1). Histopathology testing found a dense nodular infiltrate of small and large lymphocytes, histiocytes, plasma cells, and eosinophils. Immunohistochemistry findings showed that the small, CD3 lymphocytes exhibited a normal CD4:CD8 ratio. The large lymphocytes were CD20. The plasma cells were of polyclonal lineage, expressing both k or l light chains. The diagnosis of CLH was made. Complete blood count and comprehensive metabolic panel were unremarkable. Viral hepatitis and HIVresults were negative. Computed tomography of the chest, abdomen, and pelvis and a hematology/ oncology workup were normal. The CLH proved refractory to treatment with incomplete responses to clobetasol, intralesional triamcinolone, hydroxychloroquine, mycophenolate mofetil, doxycycline,

Concurrent metastases of papillary thyroid carcinoma to the scalp and Meckel’s cave

We present the case of a 65-year-old man with severe headaches and unilateral facial weakness, seen in consultation by the dermatology service to rule out primary cutaneous melanoma after brain imaging identified an enlarging mass within the right trigeminal (Meckel’s) cave. Examination revealed only a pair of erythematous papules on the scalp, for which biopsy demonstrated metastatic papillary thyroid carcinoma. Further evaluation and subsequent thyroidectomy confirmed the origin of widespread internal disease, followed by definitive excision of scalp lesions and multimodal management of systemic involvement. Whereas presentation of metastasis to the skin is highly variable, a low threshold for biopsy may allow for histological identification of internal disease not otherwise considered in the clinical differential.

Dermatologic Conditions of the Early Post-Transplant Period in Hematopoietic Stem Cell Transplant Recipients

Hematopoietic stem cell transplants (HSCTs) are used to treat a variety of conditions, including hematologic malignancies, bone marrow failure syndromes, and immunodeficiencies. Over 60,000 HSCTs are performed annually worldwide, and the numbers continue to increase. Indeed, as new conditioning regimens develop, more and more individuals, including those of older age, will be eligible for transplants. Nevertheless, although HSCTs are clearly a life-saving and necessary treatment for thousands of patients per year, there is still substantial morbidity and mortality associated with the procedure. Of note, skin eruptions in the post-HSCT period are frequent and often significantly reduce quality of life in recipients. Moreover, these cutaneous findings sometimes herald an underlying systemic condition, presenting possible opportunities for timelier intervention. Dermatologists therefore play a vital role in distinguishing life-threatening conditions from benign issues and prompting recognition of critical complications earlier in their course. This article aims to review the major dermatologic conditions occurring in the early post-HSCT period.

Hoarseness as a presentation of mycosis fungoides infiltrating the larynx

Laryngeal involvement is a rare manifestation of mycosis fungoides (MF), with only nine reported cases of cutaneous T cell lymphoma with laryngeal or vocal cord involvement. Herein, we report the case of a patient with a 7-year history of MF who presented to the emergency department with hoarseness, throat tightness and cough, as well as erythroderma and skin tumours. Laryngoscopy and CT imaging were concerning for lymphomatous involvement of the left false vocal cord. A biopsy was taken of the false vocal cord lesion, which revealed an aberrant immunophenotype consistent with MF. The patient was started on doxorubicin with initial rapid improvement in symptoms. Within 2 months, her respiratory status and skin involvement worsened. Subsequent studies showed bone marrow involvement. The patient expired 4 months after original presentation. This report describes the patient’s presentation and clinical course, and reviews the literature on vocal cord and laryngeal involvement of MF.