银屑病样表现的移植物抗宿主病1例

患儿男,5岁。躯干、四肢皮疹伴瘙痒1周。7个月前,因患"急性B淋巴细胞白血病"行异基因造血干细胞移植术,术后发生两次急性移植物抗宿主病,临床表现为绿豆大鲜红色丘疹,压之退色,疹间皮肤正常,曾予糖皮质激素或免疫抑制剂治疗,丘疹可消退。皮肤科情况:面、颈、躯干及四肢伸侧可见散在分布大小不一的圆形或椭圆形干燥性红斑,上覆白色鳞屑,指/趾甲无受累,Auspitz’s征阴性。皮损组织病理示:表皮不规则增厚,浆痂形成,灶性海绵水肿,灶性基底细胞液化,表皮内可见个别坏死角质形成细胞,真皮浅中层血管周围可见稀疏的单一核细胞浸润。诊断:银屑病样表现的慢性移植物抗宿主病。     

Photo‐induced graft‐versus‐host disease

Overlap chronic graft‐versus‐host disease (GVHD) associates both features of acute and chronic GVHD. Trigger factors for chronic GVHD are unclear. We describe two patients who received allogenic haematopoietic stem‐cell transplantation, and who later developed overlap chronic GVHD after sun exposure. Available data from in vivo investigations suggest ultraviolet B radiation (UVB) has a beneficial effect on acute and chronic GVHD. The role of sun irradiation as a trigger for isomorphic cutaneous GVHD has been rarely reported in the literature. Herein, we demonstrate for the first time, using repetitive broadband phototesting, that UVB triggers chronic GVHD.     

异基因外周血干细胞移植术后中毒性表皮松解症临床分析

目的总结异基因造血干细胞移植后中毒性表皮松解症(TEN)诊治经验。方法分析3例表现为TEN的造血干细胞移植后急性移植物抗宿主病(aGVHD)。结果3例TEN均发生于外周血干细胞移植后,表现为皮肤水疱及表皮松解,合并高热、肠炎或肝损害,经给予有效的免疫抑制剂,联合营养支持及相应护理措施,皮损均消退。结论TEN是皮肤GVHD最严重的类型,需采用针对aGVHD的免疫抑制为主的综合治疗。     

Acute follicular graft-vs-host reaction. A distinct clinicopathologic presentation

Human graft-vs-host disease (GVHD) is a life-threatening complication that may occur following allogeneic bone marrow transplantation. In acute GVHD, skin involvement is frequent, and the skin is often the initial organ involved. The rash typically is a blanchable, erythematous macular eruption. We present the first report of follicular cutaneous GVHD. Three patients developed follicular papules simulating bacterial or fungal folliculitis as a major clinical expression of cutaneous involvement in acute GVHD following allogeneic bone marrow transplantation. In each case, histopathologic examination demonstrated features of acute graft-vs-host reaction involving hair follicles. This suggests that follicular epithelium may be an early target in acute GVHD.     

Role of skin biopsy to confirm suspected acute graft-vs-host disease: results of decision analysis

OBJECTIVE: To estimate the value of skin biopsy in the evaluation of suspected acute cutaneous graft-vs-host disease (GVHD) after allogeneic stem cell transplantation. DESIGN: Decision analysis using parameters specified by expert opinion for skin biopsy characteristics, prevalence of acute GVHD, and value of potential outcomes. One-, 2-, and 3-way sensitivity analyses were performed. SETTING: Major stem cell transplantation centers in the United States. PATIENTS: Hypothetical cohort of patients with suspected acute cutaneous GVHD after stem cell transplantation. INTERVENTIONS: The following 3 interventions were compared: treat immediately for GVHD without performing a skin biopsy, perform a skin biopsy and treat immediately but stop treatment if skin biopsy specimen findings are inconsistent with GVHD, and perform a skin biopsy and await results of the skin biopsy specimen before treating. MAIN OUTCOME MEASURES: Number of patients appropriately and inappropriately treated with each intervention, consistency of physician-reported behavior, individualized decision analyses, and preferred intervention based on the aggregate estimates of respondents. RESULTS: The decision to treat immediately for GVHD without performing a skin biopsy yielded the best clinical outcome for the specified clinical setting and under the parameters specified by expert opinion. One-way sensitivity analyses showed that these conclusions are robust if the prevalence of acute cutaneous GVHD in stem cell recipients with rash is greater than 50%, if the sensitivity of skin biopsy specimen is less than 0.8, and the specificity of skin biopsy specimen is less than 0.9. Only 25% of physicians interviewed chose an intervention consistent with their estimates of prevalence, test characteristics, and outcome evaluations, indicating an opportunity to improve management of this important clinical condition. CONCLUSIONS: This decision analysis modeling technique predicts that in patient populations in which the prevalence of GVHD is 30% or greater (typical for allogeneic stem cell transplantation), the best outcomes were obtained with treatment for GVHD and no skin biopsy. In populations with prevalence of GVHD of 30% or less, obtaining a skin biopsy specimen to guide treatment was predicted to provide the best patient outcomes.     

Dermatitis espongiótica y enfermedad de injerto contra huésped

—Graft versus host disease (GVHD) is an immunological reaction of the donor's T-cells against the recipient's tissues. Acute GVHD includes the manifestations that appear in the first three months after transplantation, and fits in the microscopic pattern of interphase dermatitis or lichenoid reactions.We present the case of a 35-year-old male, who received an allogenic bone marrow transplant. He received GVHD prophylaxis with cyclosporine and methotrexate. 50 days after transplantation, he presented with a rash, with a histopathological diagnosis of spongiotic dermatitis. Fifteen days later, he presented with a worsening of the skin symptoms and alteration of the liver profile, and a new skin biopsy showed an interphase dermatitis strongly suggestive of GVHD. With the diagnosis of cutaneous grade 3 and hepatic grade 1 acute GVHD, the immunosuppressive treatment was increased, which led to gradual improvement in both sets of symptoms.As there are no clinical or histological characteristics that differentiate whether a rash during the post-transplant period is due to GVHD or to drugs, some authors advise treating the rash as GVHD, and increasing immunosuppression, as the consequences of delaying treatment may be very serious.     

Graft‐versus‐Host‐Disease: Ein interdisziplinäres Problem aus der Sicht des Dermatologen

Graft‐versus‐host disease (GVHD) is a frequent complication following hematopoietic stem cell transplantation. Acute and chronic GVHD are identified based on the onset of clinical symptoms and signs. Whereas acute GVHD is relatively uniform in its appearance, chronic GVHD is characterized by a broad spectrum of clinical manifestations. The aim of this review is to introduce the reader to the pathophysiologic processes underlying GVHD, to demonstrate its manifestations in the skin and to review current therapeutic options.     

Hyperacute graft-versus-host disease: histological assessment of skin biopsy specimens from 19 cases

Background. Hyperacute graft‐versus‐host disease (GVHD) is defined as GVHD occurring within 14 days after haematopoietic stem‐cell transplantation (HSCT). Aim. To evaluate the usefulness of skin biopsy in assessing hyperacute GVHD. Methods. We examined 19 cases of hyperacute GVHD from a total of 134 consecutive HSCT cases at Shinshu University Hospital between 1999 and 2008. Results. Exanthemas were seen in all patients, which were mainly disseminated maculopapular erythemas, commonly present in acute GVHD as well. Most patients presented with a high fever, and a few had mild hepatic dysfunction and/or diarrhoea. The clinical grade of GVHD was 1–2 in all patients; there were no cases of clinical grades 3–4. The histological findings of skin biopsy were divided into three groups: (i) eight had grade 2 changes, characterized by diffuse vacuolization of basal cells, with dyskeratotic bodies; (ii) five had grade 1 changes, characterized by vacuolization of epidermal basal cells (all these cases were diagnosed as acute GVHD with grade 2 histological changes at subsequent biopsy); (iii) and six had no significant changes (these cases were also diagnosed as acute GVHD with grade 2 (four cases) or grade 1 (one case) histological changes on the second biopsy). Many of the patients developed acute and later chronic GVHD. Conclusion. Skin biopsy should be considered when eruption develops after HSCT even before engraftment, especially when other organ involvement is minimal. If the first skin biopsy is inconclusive, follow‐up biopsy within a short time is helpful in the diagnosis of hyperacute GVHD.     

Annular plaques: An unusual manifestation of graft-versus-host disease

Chronic cutaneous graft-versus-host disease (GVHD) classically presents with lichenoid papules or sclerotic plaques. This case highlights an unusual clinical manifestation of chronic GVHD and demonstrates that the skin morphology of chronic GVHD and cutaneous lymphoma may be similar. We report for the first time a case of annular scleroderma-like graft-versus-host disease in a patient following allogeneic stem cell transplant for CD30+ anaplastic large cell lymphoma. Treatment of these skin lesions with ultraviolet A1 (UVA1) phototherapy resulted in significant improvement.     

Very late appearance of acute graft-versus-host disease after tapering immunosuppression.

Graft-versus-host disease (GVHD) is a major complication of stem cell transplantation. Here we report a 40-year-old woman who developed an acute GVHD 30 months after transplantation. Late and very late appearance of acute GVHD has only been described in rare cases.     

Late appearance of acute graft-vs-host disease after suspending or tapering immunosuppressive drugs

BACKGROUND: Graft-vs-host disease (GVHD) is divided into acute and chronic phases based on time and clinical and histological features. The criterion of 100 days after transplantation for separating acute GVHD from chronic GVHD has been challenged on the following points: (1) the lichenoid rash of chronic GVHD may be observed as early as day 31 and acute GVHD may persist after day 100 in some cases, and (2) specific histological features do not consistently separate acute from chronic GVHD defined as the number of days after transplantation. However, the appearance of acute cutaneous GVHD after day 100 is not well established. OBSERVATIONS: Three patients developed a rash with clinical and histological features of acute GVHD between days 153 and 192 after allogeneic bone marrow transplantation or peripheral blood stem cell transplantation. In all patients, the late flare of acute GVHD occurred after tapering or suspending the immunosuppressive regimen with cyclosporine or corticosteroids, and was accompanied by stigmata of chronic GVHD in other target organs. CONCLUSIONS: The rash of acute GVHD may be observed as late as 192 days after transplantation, especially after tapering or suspending the immunosuppressive drugs, and should be considered in the differential diagnosis of late erythematous eruptions after transplantation.     

Eruption of lymphocyte recovery or autologous graft-versus-host disease?

Maculopapular exanthemas have a particular high incidence among patients treated with autologous hematopoietic stem cell transplantation (HSCT). In most cases, a viral or drug induced origin is easily identified. However, the transplantation itself may also induce similar skin changes. These exanthemas are known under various names, such as autologous graft-versus-host disease (GVHD), engraftment syndrome (ES) or eruption of lymphocyte recovery (ELR). Given the clinical and histopathological similarities of these disorders, it can prove difficult to establish a diagnosis. Here, we describe a patient who developed a maculopapular exanthema after autologous stem cell transplantation for multiple myeloma, diagnosed as autologous GVHD. We also briefly review the current knowledge of the pathogenesis of autologous GVHD, ES, and ELR. Based on these data we would like to suggest that the latter two do not reflect own disease entities but rather different presentations of autologous GVHD.     

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.     

Thymoma-associated multiorgan autoimmunity: a graft-versus-host-like disease

Graft-versus-host disease (GVHD) is a T cell-mediated disease seen most commonly after hematopoietic stem cell transplantation. Rarely, a GVHD-like disease can be seen in patients with malignant thymoma. We describe a 50-year-old man with malignant thymoma who developed skin, liver, and intestinal manifestations similar to that seen in GVHD. We also review other reported cases of GVHD-like manifestations in the setting of thymoma and propose "thymoma-associated multiorgan autoimmunity" as a name for this novel disease. Specifically, thymoma-associated multiorgan autoimmunity is defined as a disease of the liver, intestine, or skin, which on histopathology resembles GVHD but is seen in the setting of malignant thymoma and not after hematopoietic stem cell transplantation.     

Eczematoid graft-vs-host disease: a novel form of chronic cutaneous graft-vs-host disease and its response to psoralen UV-A therapy

BACKGROUND: Chronic cutaneous graft-vs-host disease (GVHD) is generally classified by whether lesions have a lichenoid or sclerodermatous morphology. Other unusual clinical forms have been reported that exhibit the features of dermatomyositis and lupus erythematosus. Within a large population of individuals who underwent allogeneic stem cell transplantation because of hematologic malignancy, a group of patients was identified in whom severe and persistent eczema developed. OBSERVATIONS: We prospectively evaluated 10 adult patients with unexplained eczematous dermatosis after allogeneic hematopoietic stem cell transplantation. The dermatosis developed between 2 and 18 months (mean, 7.5 months) after receipt of the transplant, exhibited the typical clinical features of dermatitis, and became erythrodermic in each case. The patient group had strong risk factors for chronic cutaneous GVHD: 8 had received a transplant from an unrelated donor, 7 had evidence of extracutaneous GVHD, and 7 had a history of acute cutaneous GVHD. Sampling of lesional skin revealed the histologic features of GVHD coexisting with the changes of dermatitis. The patients were treated with topical corticosteroid and systemic immunosuppressive agents. Six patients also received psoralen-UV-A. Four patients achieved prolonged remission. Six patients died, 5 of infective complications and 1 of relapsed leukemia. CONCLUSIONS: The eczematous dermatosis observed represents a novel form of chronic cutaneous GVHD that we named eczematoid GVHD. Eczematoid GVHD is an aggressive, chronic dermatosis that requires substantial immunosuppression therapy to achieve control. It is associated with a poor prognosis. Although atopy can be transmitted to an individual from a hematopoietic stem cell transplant, none of the donors in this series gave a history of an atopic disorder. Therefore, other factors must be implicated in provoking the expression of an eczematous phenotype in individuals with underlying chronic graft-vs-host activity.     

Life-threatening graft-vs-host disease

Hematopoietic stem cell transplant (SCT) is considered standard therapy for a variety of malignant and nonmalignant diseases. Graft-versus-host disease (GVHD) still represents today a major complication of hematopoietic SCT. Two types of GVHD have traditionally been recognized on the basis of the time of onset following transplantation, distinct pathobiological pathways, and different clinical presentations. The acute form commonly breaks out 2 to 6 weeks after transplantation, affecting up to 60% of patients receiving allogeneic transplants from HLA identical donors. Transfer of immunocompetent donor T cells contained in the graft may undergo alloreactivity against recipient cells because of major or minor histocompatibility antigens disparities between the donor and the immunosuppressed host. Target specificity in acute GVHD involves preferential injury to epithelial surfaces of the skin and mucous membranes, biliary ducts of the liver, and crypts of the intestinal tract. Chronic GVHD affects approximately 30% to 80% of patients surviving 6 months or longer after stem cell transplantation and is the leading cause of nonrelapse deaths occurring more than 2 years after transplantation. Chronic GVHD is a multiorgan syndrome with clinical features suggesting some autoimmune diseases, and possibly both alloreactive and autoreactive T cell clones are involved in its pathophysiology. Although GVHD may convey beneficial graft-versus-leukemia/lymphoma effects, it also entails a significant risk of morbidity and mortality. Patients with mild GVHD need only minimal, if any, immunosuppressive treatment, whereas prognosis of patients with extensive disease or resistant to standard immunosuppressive treatment may be dismal. Early recognition of GVHD followed by prompt therapeutic intervention may prevent the progression to higher-grade disease and improve the outcome for patients receiving hematopoietic SCT.     

Basiliximab treatment of severe GVHD induced by donor lymphocyte infusion with interferon‐a

The development of acute graft‐versus‐host‐disease (GVHD) in recipients of donor lymphocyte infusion (DLI) is not rare and the complication is quite often fatal. We describe a severe skin GVHD patient who responded well to basiliximab. A 20‐year‐old male who received a hematopoietic stem cell transplantation at his age of 18. His fusion gene Aml1/Eto remained positive, so he was administered with DLI combined with interferon‐a (IFN‐a). Forty days after the therapy, he presented with severe skin rashes with multiple mucous membrane involvement. The skin and mucous lesions recovered after basiliximab treatment. So far, severe type of erythema multiforme in GVHD patients after DLI with IFN‐a injection is firstly reported here, together with a new alternative therapy.     

Cutaneous manifestations of graft‐versus‐host disease: role of the dermatologist

Graft‐versus‐host disease (GVHD) is the major complication of hematopoietic stem cell transplantation and is associated with high mortality in severe cases. The skin is one of the major organs affected in both acute and chronic GVHD. This review aims to elucidate the basic characteristics of GVHD, and the role and contribution of dermatologists in the care of patients with this condition.     

Lichen Striatus Occurring after Allogenic Peripheral Blood Stem Cell Transplantation in an Adult with Aplastic Anemia

Lichens striatus (LS) is an acquired, self-limiting inflammatory dermatosis that follows the lines of Blaschko. The etiology of the eruption is unknown, but several theories have been proposed with focus on environmental factors, viral infection, cutaneous injury, hypersensitivity, and genetic predisposition. We describe a 19-year-old woman who developed a unilateral linear eruption 17 months after allogenic peripheral blood stem cell transplantation. Histopathology revealed features, which were consistent with LS. To the best of our knowledge, our patient is the first case describing the appearance of LS occurring after allogenic stem cell transplantation. We speculate that this condition represents an unusual form of localized, chronic graft-versus-host disease.     

Graft-versus-Host-Disease (GvHD) �C ein Update

GvHD remains associated with significant morbidity and mortality despite new techniques for allogeneic stem cell transplantation (SCT), such as optimized conditioning regimens. Within the past ten years, the incidence of acute GvHD has remained unchanged and the incidence of chronic GvHD has even increased. The traditional classification of GvHD according to the time of clinical manifestation is now out-dated. Acute GvHD symptoms may even occur after 100 days; vice versa, primary chronic GvHD may already be observed one month after stem cell transplantation. The current classification introduced by the National Institutes of Health includes classic acute GvHD (up to 100 days), late-onset acute GvHD (after 100 days), as well as an overlap syndrome showing features of acute and chronic GvHD and classic chronic GvHD without any time limit. Diagnosis of GvHD of the skin remains difficult because of histological similarities to drug eruptions and viral exanthems. In this first part of the article the pathophysiology, classification, skin manifestations of acute and chronic GvHD and the histopathology will be presented. In a second part the prognosis, prophylaxis and therapy of GvHD will be discussed.