Narrowband ultraviolet B phototherapy in the treatment of cutaneous graft‐versus‐host disease in oncohaematological paediatric patients

Background Graft‐versus‐host disease (GVHD) represents an important complication following allogeneic bone marrow transplantation. In recent years, narrowband ultraviolet B (NB‐UVB, 311–313 nm) has been found to be a beneficial adjuvant treatment in patients refractory to first‐line immunosuppressive drugs. Objectives The aim of this study is to analyse retrospectively the clinical outcome of 10 GVHD paediatric patients treated with NB‐UVB therapy. Patients and methods Ten paediatric patients (six girls and four boys: median age 12·5 years, range 4–20) with cutaneous GVHD were enrolled in the study: five patients with chronic GVHD and five patients with an overlap syndrome GVHD. All patients had already been shown to be resistant to first‐choice immunosuppressive protocols, and were treated with NB‐UVB phototherapy until a clinical remission of skin lesions occurred. Results A complete response (absence of lesions) was achieved in 80% of the cases (eight patients) after a median number of 29 treatments, corresponding to a median of 7·5 weeks (52 days) of treatment (range 3–13 weeks), with an average cumulative dose of 28·71 J cm^?2 (range 1·02–70·38 J cm^?2). Only two patients reported a partial remission (< 18% of body surface area involved). During the follow‐up period, a complete remission after 1 year was observed in 75% of patients and after 2 years in 71% of the evaluable patients. Conclusions This study provides evidence that NB‐UVB phototherapy represents a valid second‐line treatment in paediatric patients affected by GVHD and refractory to immunosuppressive first‐line treatment.     

Thymoma‐associated multi‐organ autoimmunity: A case of graft‐versus‐host disease‐like erythroderma complicated by Good syndrome successfully treated by thymectomy

Thymoma‐associated multi‐organ autoimmunity disease (TAMA) is a rare paraneoplastic disorder, clinicopathologically similar to graft‐versus‐host disease (GVHD). Many reported cases follow a difficult course; half of them die from serious infectious diseases subsequent to immunosuppression induced by chemotherapy for unresectable thymoma, or intensive therapies including systemic steroids for complicating autoimmune diseases and GVHD‐like symptoms. We report a patient whose skin symptoms were improved subsequently to total thymectomy. The patient also presented with hypogammaglobulinemia, which led to the diagnosis of complicated Good syndrome. Taking account of her immunodeficient condition, antibiotics and i.v. immunoglobulin were administrated promptly on onset of bacterial pneumonia, which was successfully treated. According to a review of the published work, treatments with systemic steroids for skin symptoms have limited effects and may contribute to serious infection. Our case indicates that successful treatment of thymoma itself may lead to the amelioration of the disease. The management priority should be given to the treatment of thymoma and the control of subsequent immune abnormality other than GVHD‐like erythroderma.     

Extracorporeal photopheresis in graft‐versus‐host disease

Graft‐versus‐host disease (GvHD) is a common and often serious complication of hematopoietic stem cell transplantation. There are two major forms of GvHD: an acute form which develops in the first 100days after HSCT, and a chronic form which develops later. Chronic GvHD is a multiorgan syndrome with many features of autoimmune diseases, such as sclerodermatous skin changes, cholestasis, pulmonary fibrosis, xerostomia, oral ulcerations, myositis and fasci‐itis. Unlike acute GvHD which is characterized by acute alloreactivity,the etiology of chronic GvHD is controversial and is believed to be either an extension of acute GvHD and/or a result of dysfunctional immune reconstitution with generation of autoantibodies and autoreactive T‐cell clones. GvHD is usually treated with corticosteroids and other immunosuppressants which do not always succeed in arresting its evolution. Extracorporeal photochemotherapy has been used in patients with both acute and chronic GvHD.     

The challenge of follow-up in narrowband ultraviolet B phototherapy

BACKGROUND: The use of narrowband ultraviolet (UV) B phototherapy to treat psoriasis and other disorders has increased markedly since the TL-01 lamps were introduced in the 1980s. While broadband UVB phototherapy has generally been considered to be a relatively safe treatment, some concern has been raised about the potential increased skin cancer risk with narrowband UVB. OBJECTIVES: The likelihood of a patient who is free of nonmelanoma skin cancer (NMSC) at the start of phototherapy developing a malignancy after a certain follow-up period will be dependent not only on the carcinogenic potential of the treatment but also on the age-conditional probability of natural occurrence. We were interested to explore the potential difficulty of designing studies to separate these two events. Methods Mathematical models were developed that combined age-conditional probabilities of developing NMSC due to natural causes with the risk of inducing these cancers from narrowband UVB phototherapy in order to estimate the excess number of cancers resulting from this therapeutic intervention in a cohort of patients. RESULTS: Within-department studies will be most unlikely to demonstrate that the number of NMSCs observed in follow-up studies is significantly different from that expected in an untreated population, even for a follow-up period of 20 years. CONCLUSIONS: Determination of the carcinogenic potential associated with narrowband UVB will require large multicentre studies typically involving several thousand new patients per year and followed up for 10 years or more.     

Acute cutaneous graft‐versus‐host disease resembling type II (atypical adult) pityriasis rubra pilaris

We present a case of cutaneous acute graft‐versus‐host disease (aGVHD) with confluent erythematous perifollicular hyperkeratosis and ichthyosiform scale in the clinical pattern of type II (atypical adult) pityriasis rubra pilaris (PRP), which developed 26 days after allogeneic peripheral blood stem cell transplant. Skin histology confirmed features of both aGVHD and PRP. The skin lesions were refractory to oral prednisolone and cyclosporine and only partially responsive to a combination of i.v. methylprednisolone, oral tacrolimus, oral mycophenolate mofetil, and infusions of anti‐thymocyte globulin and the tumour necrosis factor‐α inhibitor, etanercept.     

Remission period in psoriasis after multiple cycles of narrowband ultraviolet B phototherapy

The aim of this study was to investigate the duration of remission periods in psoriasis after narrowband ultraviolet B (NB‐UVB) phototherapy, especially during multiple cycles of treatment. We analyzed 63 patients (101 cases) demonstrating marked improvement after NB‐UVB phototherapy. The remission period was defined as the duration of time from the end of phototherapy until treatment using either phototherapy or systemic treatments was required again. It was found that an age of 60 years or older, history of systemic therapy within 6 months and three or more phototherapy cycles were significantly associated with shorter remission periods. Furthermore, multivariate analysis confirmed that three or more phototherapy cycles (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.73–9.33; P = 0.001) and a history of systemic therapy (OR, 2.2; 95% CI, 1.27–3.95; P = 0.005) were independently associated with the shorter remission period. In conclusion, when planning NB‐UVB phototherapy for psoriatic patients who have undergone multiple phototherapy cycles, clinicians should consider the possibility of shorter remission periods.     

A question of persistence: Langerhans cells and graft‐versus‐host disease

Langerhans cells (LCs) have been scrutinized many times in studies of the pathogenesis of graft‐versus‐host disease (GVHD). As migratory dendritic cells, LCs are capable of direct antigen presentation to cytotoxic T cells. Their self‐renewal capacity has led to speculation that persistent recipient LCs could provide a continuous source of host antigen to donor T cells infused during hematopoietic stem cell transplantation (HSCT). In this issue of Experimental Dermatology, a new study examines at the relationship between recipient LCs and chronic GVHD.     

Basement membrane antibodies in sera of haematopoietic cell recipients are associated with graft‐versus‐host disease

Background Graft‐versus‐host disease (GvHD) occurs frequently after haematopoietic cell transplantation (HCT). Mucocutaneous lesions of GvHD may mimic bullous autoimmune dermatoses, and 10 cases of concurrent GvHD and a bullous autoimmune disease have been reported in the literature. Objective To determine the frequency of circulating antibodies to the cutaneous basement membrane zone (BMZ) in HCT patients with GvHD in comparison with HCT patients without GvHD, psoriasis patients and healthy controls. Subjects and methods We examined 42 patients with chronic GvHD, 18 HCT patients without GvHD, 11 psoriasis patients and 40 healthy controls, prospectively. Sera were tested by indirect immunofluorescence (IIF) on salt‐split skin, NC16a‐ELISA and immunoblot using keratinocyte extracts. Univariate statistical analyses and logistic regression were performed to assess possible correlations of graft and patient characteristics with the presence of BMZ antibodies. Results Circulating basement membrane zone (BMZ) antibodies were detected in 10/42 (24%) GvHD sera by immunoblot, but not in any of the HCT sera from patients without GvHD (0/18; 0%). The antibodies targeted collagen VII, BP230, collagen XVII/BP180 or p200/laminin γ1. Clinically manifest bullous autoimmune dermatoses (bullous pemphigoid or epidermolysis bullosa acquisita) were found in two GvHD patients. 1/11 (9%) psoriasis sera and 1/40 (2.4%) healthy control sera reacted with collagen XVII or BP230, respectively. Conclusions Circulating BMZ antibodies are significantly associated with chronic GvHD in contrast to uncomplicated HCT. Recurrent mucocutaneous lesions in chronic inflammatory skin disorders may liberate antigens, which may lead to production of BMZ antibodies, particularly in the context of GvHD‐mediated reduced self‐tolerance.     

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.     

Phototherapy for the treatment of cutaneous graft versus host disease

Graft versus host disease (GvHD) occurs in half the patients who receive allogenic haematopoietic stem cell transplantation and is a major contributor for the morbidity and mortality in these patients. Immunosuppressant therapy cannot suppress all the manifestations of GvHD and new ways of treating the condition are needed. The focus of this review is the treatment of cutaneous GvHD through phototherapy. Of the six acute and ten chronic cutaneous GvHD case series examined the overall trend was that phototherapy was able to reduce the presence of cutaneous lesions of GvHD and, as a consequence, steroid use could be reduced. This provides a positive outlook for phototherapy as a treatment for cutaneous GvHD but there is a need for future studies to include larger numbers of patients in order to obtain more data.     

A comparison of three times vs. five times weekly narrowband ultraviolet B phototherapy for the treatment of chronic plaque psoriasis

Background: Narrowband ultraviolet B (NB-UVB) phototherapy is an effective treatment for psoriasis.
Objectives: To compare the effects of three and five times weekly NB-UVB phototherapy in the treatment of chronic plaque psoriasis.
Methods: Sixty-five patients with chronic plaque psoriasis were allocated to receive three or five times weekly NB-UVB, starting at low dose.
Results: Among the patients who completed the study, clearance was achieved in 18 out of 23 patients (78%) in the three times weekly group and in 15 out of 22 patients (68%) in the five times weekly group. The difference was not statistically significant ( P =0.44).
No statistically significant differences were found between the two groups in the number of treatments ( P =0.95), cumulative UVB dose ( P =0.51), and rate of side-effects. Length of the treatment period was significantly shorter in the five times weekly group ( P <0.001). At the end of treatment, the mean psoriasis area and severity index score was lower in the three times weekly group ( P =0.02).
Conclusions: We recommend three times weekly NB-UVB for chronic plaque psoriasis; however, the more rapid clearance of psoriasis with five times weekly phototherapy may justify using this method in some patients.     

Psoriasiform graft‐versus‐host disease distributed along Blaschko's lines

This case presents an unusual manifestation of cutaneous chronic graft‐vs‐host disease (cGVHD) mimicking psoriasis along Blaschko's lines. Such a presentation may pose a particular challenge to providers as it is quite rarely reported, and, therefore, it is possibly misdiagnosed. cGVHD may mimic psoriasis and should be considered in any patient previously transplanted even with a previous history of psoriasis. A Blaschkoid pattern of cGVHD is unusual and may be the manifestation of an immune reaction unveiling a previously masked mosaicism.     

Cutaneous non‐tuberculous mycobacterial infection in patients with chronic graft‐versus‐host disease: A case series

We report the first case series of allogeneic haematopoietic stem‐cell transplant patients with graft versus host disease who developed cutaneous non‐tuberculous mycobacteria infection. A multidisciplinary approach, reduction of immunosuppressive medications, combination of antibiotics, close skin surveillance and excision of suitable lesions are recommended in this specific subgroup.     

Nailfold capillary abnormalities are prevalent in sclerodermoid graft‐versus‐host disease and readily detected with dermatoscopy

Background Well‐recognized videocapillaroscopic patterns have been described in systemic sclerosis (SS). However, no studies have described the capillary abnormalities of sclerodermoid chronic graft‐versus‐host disease (Scl GVHD) developed after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). Objectives The aims of this study were to find the characteristics of nailfold capillary changes in Scl GVHD after allo‐HSCT. Patients and methods Eighteen patients affected by Scl GVHD and a control group of 15 patients with lichenoid GVHD were evaluated. Duration and type of sclerodermoid GVHD, Raynaud phenomenon (RP), dysphagia, joint contractures, antinuclear antibodies (ANA), anti‐Scl‐70 and anticentromere (ACA) antibodies were investigated parameters. A nailfold capillary examination using a standard dermatoscope was performed on all fingers of each subject. Results Twelve patients were male and six were female with a mean age of 37 ± 11·6 years. Joint retractions and dysphagia developed in 27·8% and 38·9% of the patients, respectively. Three (16·7%) patients had RP. Autoimmune markers like anti‐Scl‐70 and ACA were negative in all. Capillaroscopy was abnormal in 15 patients with Scl GVHD. A regular disposition of the capillary loops along with avascular whitish linear areas at the level of the last row, neovascularization with reticular pattern, capillary disorganization, haemorrhages, enlarged capillaries and avascular areas were the main features. No capillary abnormalities were observed in patients with lichenoid GVHD. There was no statistically significant correlation between ANA positivity, RP, joint retractions, dysphagia, extensiveness of Scl GVHD, duration of sclerodermoid lesions and nailfold capillaroscopy analysis. Conclusions This study shows the identification of distinct nailfold capillaroscopy patterns in patients with Scl GVHD but it does not confer special risk for any other specific clinical symptoms of the disease.     

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.