Treatment of antiviral‐resistant recurrent erythema multiforme with dapsone

Recurrent erythema multiforme (REM) is a chronic disease characterized by frequent episodes of target cutaneous lesions in an acral distribution. Conventional treatment includes systemic corticosteroids and antiviral therapy. The aim of this study was to evaluate dapsone as a potential steroid sparing‐agent for the treatment of REM after a failed trial of at least one antiviral therapy (acyclovir, famciclovir, or valacyclovir). A retrospective chart review was conducted on thirteen patients with a diagnosis of REM who underwent treatment with dapsone after failing at least one antiviral therapy. Out of 13 patients, 6 showed complete response (CR) and 5 showed partial response (PR). The underlying cause was identified in 5 patients with all showing at least PR. Adverse effects, observed in 4 patients, included fatigue, macrocytic anemia, anxiety, insomnia and involuntary movements, and drug‐induced lupus erythematosus. A continuous course of dapsone, titrated up from 25 mg/day to a dose at which clinical improvement is seen with acceptable patient tolerance, is a viable steroid sparing‐agent for REM treatment after a failed trial of antiviral therapy.     

Hematopoietic stem cell transplantation for cutaneous T‐cell lymphoma: Summary of 11 cases from two facilities in Japan and Brazil

Some patients with cutaneous T‐cell lymphoma (CTCL) show a miserable clinical course and the only option that can induce long‐term remission for advanced CTCL may be hematopoietic stem cell transplantation (HSCT). So far, studies on HSCT for CTCL patients have been limited. In this study, we summarized 11 cases with CTCL treated with HSCT, including nine cases in Japan and two cases in Brazil. The patients were five cases with mycosis fungoides (MF), two cases with Sézary syndrome (SS), three cases with anaplastic large cell lymphoma, and one case with primary cutaneous peripheral T‐cell lymphoma, not otherwise specified (PTL‐NOS). Currently, seven out of 11 cases are alive (at 13–108 months after transplantation) and four died at 15 days to 14 months after transplantation. When focusing on the eight patients who received allogeneic HSCT for MF/SS and PTL‐NOS, all four patients at 45 years old or under are alive at present. One case showed relapse in the skin. On the other hand, one out of the other four patients at over 45 years old survived. Engraftment failure was seen in one case and all the other three cases experienced relapse. Although this is only a case series with a small number, our study has suggested that we should be careful about age when treating patients with MF/SS by allogeneic HSCT.     

Erythema multiforme: Differences between HSV‐1 and HSV‐2 and management of the disease—A case report and mini review

Erythema multiforme (EM) is an immune‐mediated reaction characterized by target lesions and with possible mucosal involvement. Its most frequent cause is HSV, with HSV‐1 more common than ?2. It is usually self‐limited but it can show recurrences. We report a peculiar case of recurrent herpes‐associated erythema multiforme (HAEM) in a 35‐year‐old man. The patient was affected by both herpes labialis and genitalis, but the typical target lesions were only associated with recurrent herpes labialis. Here, we hypothesize about the pathogenic differences between HSV‐1 and HSV‐2, and discuss the therapeutic management of HAEM.     

Hematopoietic stem cell transplantation in advanced cutaneous T‐cell lymphoma

We retrospectively reviewed data pertaining to five patients with cutaneous T‐cell lymphoma (CTCL) who had received hematopoietic stem cell transplantation (HSCT) between 2004 and 2015 at Kurume University Hospital, along with their clinical data until March 2016. For patients with advanced CTCL eligible for HSCT, autologous HSCT was performed when they responded well to chemotherapy, and allogeneic HSCT was selected for patients with advanced mycosis fungoides (MF)/Sézary syndrome (SS) and CTCL other than MF/SS with poor chemosensitivity. Two patients (primary cutaneous anaplastic large cell lymphoma and primary cutaneous CD8⁺ aggressive epidermotropic cytotoxic T‐cell lymphoma) who responded well to chemotherapy received autologous HSCT: one patient was alive in partial remission and the other died due to therapy‐related acute myeloid leukemia without disease relapse. In the remaining three patients with MF or SS, allogeneic HSCT was performed. Although one patient with MF died due to disease progression, the remaining two patients were alive in complete remission. Although there were two deaths in this study, the outcomes were considered satisfactory.     

Tularemia‐induced erythema multiforme minor in an 11‐year‐old girl

Tularemia is a rare and potentially life‐threatening infection caused by the highly infectious gram‐negative coccobacillus Francisella tularensis. We present the case of an 11‐year old girl who presented with erythema multiforme minor in the setting of an indolent but progressive soft tissue infection and was found to have tularemia. We review the role of dermatologists in identifying the features of and complications associated with this rare zoonosis and discuss the potential effect of climate change on its incidence.     

Erythema multiforme‐like cutaneous lesions in monomorphic epitheliotropic intestinal T‐cell lymphoma: a rare case report

Monomorphic epitheliotropic intestinal T‐cell lymphoma (MEITL), also known as Type II enteropathy‐associated T‐cell lymphoma (EATL), is an aggressive peripheral T‐cell lymphoma. EATL generally presents in adults with gastrointestinal symptoms. Skin involvement is very rare, found only in approximately five percent of patients. The authors report a 67‐year‐old Asian male who presented with chronic diarrhea and developed erythema multiforme‐like cutaneous lesions. A skin biopsy revealed extensive pagetoid spread of atypical lymphocytes in the epidermis. The results of an immunohistochemistry test led to a diagnosis of MEITL. This report points to the need for dermatologists and dermatopathologists to consider a possible diagnosis of MEITL when encountering similar cases.     

Origin of Langerhans cells in normal skin and chronic GVHD after hematopoietic stem‐cell transplantation

Chronic graft‐versus‐host disease (cGVHD) is a common complication following allogeneic stem‐cell transplantation (SCT). Past studies have implicated the persistence of host antigen‐presenting cells (APCs) in GVHD. Our objective was to determine the frequency of host Langerhans cells (LCs) in normal skin post‐SCT and ask if their persistence could predict cGVHD. Biopsies of normal skin from 124 sex‐mismatched T‐cell‐replete allogenic SCT recipients were taken 100 days post‐transplant. Patients with acute GVHD and those with <9 months of follow‐up were excluded and prospective follow‐up information was collected from remaining 22 patients. CD1a staining and X and Y chromosome in‐situ hybridization were performed to label LCs and to identify their host or donor origin. At 3 months, 59 ± 5% of LCs were host derived. The density of LCs and the proportion of host‐derived LCs were similar between patients that did or did not develop cGVHD. Most LCs in the skin remained of host origin 3 months after SCT regardless of cGVHD status. This finding is in line with the redundant role of LCs in acute GVHD initiation uncovered in recent experimental models.     

Psychosocial aspects of hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) has become a conventional and potentially curative treatment for various hematological diseases. As more sophisticated procedures have been developed and mortality rates have decreased, attention has shifted to the psychosocial challenges associated with transplantation. The psychosocial difficulties accompanying transplantation are addressed in the context of both quality of life (QOL) and psychopathological research. Among the psychiatric comorbidities of HSCT, anxiety, depression, sleep and sexual disorders, delirium and post-traumatic stress disorder are the most studied conditions. Recently, more attention has been focused on the psychosocial burden of caregivers. Devising recommendations for the management of psychiatric symptoms and psychosocial interventions in HSCT sufferers and close relatives is a major concern to consultation–liaison psychiatrists and transplant teams. This review synthesizes and critically evaluates the current literature on the psychosocial aspects of HSCT and appraises the clinical significance of these outcomes. Issues of QOL assessment; psychosocial functioning and QOL in the course of HSCT; impact of graft-versus-host disease and other predictors of QOL and psychosocial functioning; comorbid psychiatric disorders; and interventions to maintain or improve QOL and reduce psychopathology and psychosocial burden on family members are presented.     

Review of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in solid tumors excluding breast cancer

Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitive. Recently, oncologists have focused on the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning (RIC) for the treatment of some refractory solid tumors. After the demonstration of allogeneic graft-versus-leukemia effect in patients with hematological malignancies who received allo-HSCT, investigators evaluated this effect in patients with refractory metastatic solid tumors. According to data from experimental animal models and preliminary clinical trials, a graft-versus-tumor (GvT) effect may also be observed in the treatment of some solid tumors (e.g., renal cell cancer, colorectal cancer, etc.) after allo-HSCT with RIC. The use of RIC regimens offers an opportunity of achieving full-donor engraftment with GvT effect, as well as, a reduced transplant-related mortality. Current literature suggests that allo-HSCT with RIC might become a choice for elderly and medically fragile patients with refractory metastatic solid tumors.     

自体外周造血干细胞移植治疗成人皮肌炎一例

目的 探讨自体外周造血干细胞移植治疗成人皮肌炎的疗效.方法 1例21岁皮肌炎患者接受自体外周造血干细胞移植,随访6年.采用重组人粒细胞集落刺激因子动员外周造血干细胞后,予以环磷酰胺、甲泼尼龙、环孢素预处理,干细胞回输第3天开始使用兔抗人T淋巴细胞免疫球蛋白.观察症状体征、生化指标、造血重建及免疫恢复情况.结果 出院时皮疹明显好转,后逐渐消退;四肢肌力由移植前Ⅳ级转为Ⅴ级并持续至今;移植后肌酸激酶显著下降,但又逐渐恢复到移植前水平;回输当天开始出现白细胞下降,第8天恢复正常造血功能.移植前后免疫功能均正常.结论 对复杂难治性重症皮肌炎,可选择白体外周造血干细胞移植治疗.     

Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: Prophylaxis and treatment controversies

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, is a major complication of hematopoietic stem cell transplantation and it carries a high mortality. Prophylaxis for hepatic VOD is commonly given to transplant recipients from the start of conditioning through the early weeks of transplant. However, high quality evidence from randomized controlled trials is scarce with small sample sizes and the trials yielded conflicting results. Although various treatment options for hepatic VOD are available, most have not undergone stringent evaluation with randomized controlled trial and therefore it remains uncertain which treatment offers real benefit. It remains controversial whether VOD prophylaxis should be given, which prophylactic therapy should be given, who should receive prophylaxis, and what treatment should be offered once VOD is established.     

Cutaneous gamma/delta T‐cell lymphoma

Only 40 cases of primary cutaneous gamma/delta T‐cell lymphoma (GD‐TCL) have been described. GD‐TCL was included as a provisional entity in the WHO‐EORTC classification of cutaneous lymphomas in 2005. GD‐TCL often failed to respond to polychemotherapy and radiation therapy and have a poor prognosis with a mean survival of only 15 months. We present a patient treated with surgery, immunomodulatory therapy, and polychemotherapy. He then received hematopoietic stem cell transplantation and has been in complete remission since. Allogeneic stem cell transplantation appears to be a promising therapeutic option for aggressive and generally fatal lymphomas like GD‐TCL.     

Cytomegalovirus reactivation after autologous stem cell transplantation in myeloma and lymphoma patients: A single-center study

AIM: To determine the incidence of and the risk factors for cytomegalovirus (CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation (ASCT).METHODS: A total of 327 consecutive non CD34⁺ selected autografts performed from the Hematology and Stem Cell Transplantation Unit of Regina Elena National Cancer Institute of Rome (Italy) in the period comprised between January 2003 to January 2015, were reviewed. Over the 327 autografts, 201 were performed in patients with multiple myeloma, whereas the remaining 126 in patients affected by non-Hodgkin’s lymphoma and Hodgkin’s lymphoma. The patients who underwent an ASCT for an acute leukemia (n = 20) in the same period were excluded from this analysis. CMV DNA load in the blood has been determined by polymerase-chain reaction in the case of a clinical suspicion of reactivation, therefore, no routine monitoring strategy was adopted. In the presence of signs and symptoms of CMV reactivation an antiviral treatment was performed.RESULTS: Overall, 36 patients (11%) required a specific antiviral treatment for a symptomatic CMV reactivation (n = 32) or an end-organ disease (n = 4). We observed 20 and 16 cases of CMV reactivation among lymphoma (16%) and myeloma patients (8%), respectively. Among cases of end-organ disease, 3 were diagnosed as interstitial pneumonia and one remaining case as hemorrhagic enteritis. All cases of CMV reactivation were observed in IgG seropositive patients, with no documented cases of primary CMV infection. All patients were treated with a specific antiviral therapy, with a global rate of hospitalization of 55%; four patients received intravenous immunoglobulins. Transplant-related mortality was significantly higher in patients who experienced a CMV reactivation (8.4% ± 4.7% vs 1.7% ± 0.8%; P = 0.047). In univariate analysis, a pre-transplant HBcIgG seropositivity, a diagnosis of T-cell non-Hodgkin’s lymphoma and higher median age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection requiring specific antiviral therapy (P < 0.001, P = 0.042 and P = 0.004, respectively). In multivariate analysis, only a pre-transplant HBcIgG seropositivity (OR = 8.928, 95%CI: 1.991-33.321; P = 0.023) and a diagnosis of T-cell non-Hodgkin’s lymphoma (OR = 4.739, 95%CI: 1.511-11.112; P = 0.042) proved to be independent predictors of a post-transplant clinically relevant CMV reactivation.CONCLUSION: A symptomatic CMV infection can occur in about 11% of adult patients with lymphoma or myeloma undergoing ASCT. A pre-transplant HBcIgG seropositivity and a diagnosis of T-cell non-Hodgkin’s lymphoma should be considered as independent predictor factors of CMV reactivation.     

Erythema multiforme‐like eruption associated with plant‐induced allergic contact dermatitis in a pediatric patient: A case report

An 11‐year‐old boy presented to the emergency department 5 days after playing in the forest. His initial eruption, consistent with allergic contact dermatitis to poison ivy, progressed into target lesions involving his extremities, palms, upper trunk, and face, consistent with an erythema multiforme‐like eruption. This report details the case and reviews the literature concerning this atypical and potentially underreported complication of plant‐induced allergic contact dermatitis.     

Unexpected recalcitrant course of drug‐induced erythema multiforme‐like eruption and interstitial pneumonia sequentially occurring after nivolumab therapy

Vemurafenib improves survival of melanoma patients. However, cutaneous side‐effects commonly occur in them. Nivolumab and ipilimumab are monoclonal antibodies against programmed death 1 and cytotoxic T‐lymphocyte‐associated antigen 4, both of which regulate excessive T‐cell activation. Although these agents induce antitumor immunity against melanoma, the modified immune condition may result in an unexpected adverse reaction which has not been observed previously. Herein, we report a case who manifested severe erythema multiforme‐like eruption with mucosal involvement associated with vemurafenib following nivolumab. The patient also subsequently suffered from ipilimumab‐induced interstitial pneumonia with refractory course. Such a case has never been reported. This case suggested that dermatologists should pay special attention to unexpected adverse events of these drugs, and carefully observe cutaneous and respiratory status of patients during the treatment of melanoma.     

Granuloma annulare on herpes zoster scars in a Hodgkin''s disease patient following autologous peripheral stem cell transplantation

Various cutaneous lesions including granulomatous reactions may occur at sites of resolved herpes zoster infection. A 46-year-old man with Hodgkin's disease developed localized granuloma annulare lesions on herpes zoster scars 3 months after allogeneic peripheral stem cell transplantation. This is the first case of granuloma annulare localized on herpes zoster scars that developed following peripheral stem cell transplantation.