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.     

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.     

PUVA therapy for chronic cutaneous graft-vs-host disease

Chronic graft-vs-host disease (GVHD) is an immunologic disorder frequently occurring as a late sequelae of allogeneic bone marrow transplantation and characterized in the skin with lichenoid or sclerodermoid lesions. Systemic immunosuppressive agents such as corticosteroids or cyclosporine are usually required to control the disease. Therapy with psoralen and UVA (PUVA) has recently been shown to be effective for skin and oral mucosa in a few cases of GVHD. We present our experience with PUVA in six patients, five with lichenoid and one with sclerodermoid GVHD. None of these patients had significant systemic involvement. All five patients with lichenoid GVHD showed clinical improvement after PUVA therapy. Three of these patients had complete clearance of skin lesions. Clinical clearance of the disease was accompanied by microscopic clearance. The patient with sclerodermoid GVHD did not respond to therapy. No significant complications or exacerbation of systemic disease occurred. We confirm that PUVA is an effective and safe therapy for the cutaneous manifestations of lichenoid chronic GVHD. We postulate that PUVA therapy clears chronic lichenoid GVHD by selective cytotoxicity for the activated lymphoid cells in the inflammatory infiltrate.     

Pediatric Pemphigus Vulgaris: Durable Treatment Responses Achieved with Prednisone and Mycophenolate Mofetil (MMF)

Abstract: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease of the skin and mucous membranes. Most cases occur in adults; cases in children are rare. This report describes the clinical presentations and treatment responses of three children with PV, as confirmed according to histology and indirect immunofluorescence studies. In all three cases, oral prednisone used in conjunction with mycophenolate mofetil (MMF) resulted in complete clinical remission, during which all pharmacotherapy was successfully discontinued. Resolution of the skin and mucosal blistering tended to occur quickly with prednisone, and after initiation of treatment with MMF, discontinuation of all pharmacotherapy was achieved within a range of 10 to 30 months in the three patients. One patient experienced a recurrence of genital lesions 19 months after discontinuation of therapy, but the condition remitted within 2 weeks with topical corticosteroid therapy. At the time of this report, the duration of complete remission ranged from 6 to 19 months. In summary, combination therapy with prednisone and MMF for pediatric PV appears to be a safe and effective approach that is associated with durable remission.     

Azathioprine. An effective, corticosteroid-sparing therapy for patients with recalcitrant cutaneous lupus erythematosus or with recalcitrant cutaneous leukocytoclastic vasculitis

Azathioprine sodium has been reported to be effective therapy for chronic cutaneous lupus erythematosus (LE) but rarely for chronic cutaneous leukocytoclastic vasculitis (LV). We used azathioprine in the treatment of six patients with cutaneous LE, four of whom had subacute cutaneous (nonscarring) LE and two of whom had chronic cutaneous (scarring, discoid) LE, and six patients with chronic cutaneous LV. The conditions of all patients had been resistant to conventional therapy, and they required long-term oral corticosteroid therapy for control of their disease. Two of the patients with LE had prominent palmar and/or plantar involvement. Three patients with LE had an excellent response to azathioprine, with near complete clearing of the skin lesions, allowing a decrease in prednisone dosage. One patient with LE initially demonstrated significant improvement, but azathioprine therapy had to be discontinued because of pancreatitis. The treatment failed in two patients with LE; one had nausea and the other repeatedly developed a drug-induced fever. Five of the six patients with LV had improved conditions, with complete control of the disease occurring in two patients and partial control in three patients. Azathioprine is effective for some patients with cutaneous LE and chronic cutaneous LV, but it should be reserved for patients with severe disease in whom more conventional treatment fails.     

Clinical manifestations of cutaneous graft-versus-host disease after allogeneic haematopoietic cell transplantation: long-term follow-up results in a single Turkish centre

The aim of this study was to evaluate the clinical manifestations of cutaneous graft-versus-host disease (GVHD) developed after allogeneic haematopoietic cell transplantation. In all, 67 patients were evaluated: 49 patients developed acute GVHD, 17 patients developed de novo chronic GVHD and 29 developed secondary chronic (15 limited, 14 progressive) GVHD following acute cutaneous GVHD. Of the 46 patients with chronic GVHD, lichenoid lesions were observed in 32 and sclerodermoid lesions were observed in 12. In four patients with sclerodermoid cutaneous GVHD, these lesions occurred after a lichenoid phase. Oral lesions were present in 61% of the patients and six of them had only oral mucosal involvement without any skin lesions. Nail lesions were observed in 31% of the patients. During the follow-up period 15 patients with GVHD died and in 7 of them the cause of death was related to chronic GVHD. In conclusion, GVHD has a wide spectrum of cutaneous manifestations, which can be used as an important tool for the early diagnosis of the disease.     

硬皮病样皮肤移植物抗宿主病24例临床特征分析

目的:分析异基因造血干细胞移植后硬皮病样皮肤移植物抗宿主病（GVHD）的临床特征和危险因素。方法:回顾2014—2019年间就诊于北京大学人民医院皮肤科硬皮病样皮肤GVHD患者24例的临床资料,分析临床特征、治疗、预后及发展为硬皮病样皮肤GVHD的可能因素。结果:24例硬皮病样皮肤GVHD患者中男11例,女13例,年龄...     

Mycophenolate mofetil: A new therapeutic option in the treatment of blistering autoimmune diseases

Background: Mycophenolate mofetil (MMF), an ester of mycophenolic acid (MPA), was approved by the Food and Drug Administration in 1995 and is currently primarily indicated for the prophylaxis of rejection in renal transplant patients. The drug seems also to be of value in the treatment of psoriasis and rheumatic arthritis. Recently there have been 6 reported cases of successful treatment of blistering autoimmune diseases with MMF in combination with high dose prednisone therapy. Objective: On the basis of these reports we administered this new treatment regimen to several patients with blistering autoimmune diseases. Besides using a combination of MMF and high-dose prednisone we wanted to evaluate whether MMF monotherapy is also effective in the treatment of blistering autoimmune diseases. Methods: We administered MMF to 5 patients who had severe pemphigus vulgaris or bullous pemphigoid. Two patients received MMF in combination with high-dose prednisone therapy and 3 patients received MMF monotherapy. To our knowledge, this is the first report of successful treatment of pemphigus vulgaris and bullous pemphigoid with MMF monotherapy. Results: All patients were completely free of symptoms within 8 to 11 weeks of therapy. Patients who had received MMF monotherapy responded as well to treatment as those who received a combination of MMF and high-dose prednisone. Conclusion: Our experiences strongly suggest that MMF monotherapy may be effective for patients even with severe pemphigus vulgaris and bullous pemphigoid. In addition, MMF monotherapy, at least over the short term, offers the advantage of fewer side effects in comparison to immunosuppressive combination therapy and was well tolerated by our patients. (J Am Acad Dermatol 1999;40:957-60.)     

Severe chronic actinic dermatitis treated with cyclosporine: 2 cases

INTRODUCTION: The treatment of the severe forms of photodermatoses often requires potent systemic immunosuppressive drugs. We report two patients suffering from severe photodermatitis successfully treated with oral cyclosporine. CASES REPORT: A 58-year-old man developed severe pruritic eczematous reactions for several years on light-exposed and light-protected skin following each sun exposure. A 66-year-old man showed similar lesions restricted to the head and neck. The clinical presentation and evolution as well as histologic, immunohistologic, allergologic and photobiologic assessments suggested the diagnosis of actinic reticuloid and persistent light reactivity, respectively. The lesions of both patients did not respond to a high dose regimen of systemic corticosteroids (methylprednisolone 1 mg/kg/day) for several weeks. The severity of cutaneous lesions and pruritus required another potent immunosuppressive treatment. Oral cyclosporine at the maximum daily dose of 4 mg/kg was given for three months. A rapid improvement of the pruritus and skin lesions occurred in the two patients, without significant side-effect. The first patient experienced recurrent lesions after termination of cyclosporine treatment during summer time. The other patient did not develop new skin eruption for 3 years after stopping the initial treatment with cyclosporine. DISCUSSION: Low-dose oral cyclosporine is a quick-acting and well tolerated symptomatic treatment of severe photodermatoses resistant to other systemic immunosuppressive drugs. However, therapeutic results do not consistently exhibit long-standing remanent effect.     

Successful treatment of subacute cutaneous lupus erythematosus with mycophenolate mofetil

Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been shown to be effective in transplant patients. Some case reports and pilot studies have suggested efficacy against systemic lupus erythematosus (LE), particularly in the case of lupus nephritis. Reports on MMF treatment of skin manifestations of LE are still anecdotal. We report two cases with extensive skin lesions owing to subacute cutaneous LE (SCLE). Both patients had been treated with azathioprine and antimalarials without effect. Finally both patients were given highly dosed glucocorticosteroids, which were also ineffective but led to vertebral fractures because of long-term steroid treatment in one patient and steroid-induced psychosis in the other. MMF 2 g daily caused the skin manifestations to disappear within a few weeks in both patients. One patient was followed up for more than 24 months, and showed good toleration of MMF treatment. The skin remained stable over this period when at least 1 g MMF per day was administered. In conclusion, MMF appears to be an attractive treatment option in skin manifestations of SCLE, and seems to be beneficial for patients with steroid-refractory lesions that are also resistant to treatment with immunosuppressants or antimalarials. The observations suggest that further evaluation of this route in randomized controlled trials is warranted.     

Dermatologic Treatment of Cutaneous Graft Versus Host Disease

Cutaneous involvement in graft versus host disease (GVHD) after allogeneic hematopoietic cell transplant can be separated into acute GVHD (aGVHD), lichenoid chronic GVHD (cGVHD) and sclerodermatous cGVHD. It seems clear that these syndromes result from different mechanisms and entail different treatment approaches. Standard treatment of cutaneous aGVHD involves the intensification of immunosuppressive therapy with adequate topical supportive management. In skin-limited disease, phototherapy has shown promising results. In cutaneous cGVHD, the combination of corticosteroids and cyclosporine (ciclosporin) is the recommended therapy, and other immunosuppressants may be added depending on whether lichenoid or sclerodermatous lesions are present. High response rates to phototherapy have been found in lichenoid disease, while sclerodermatous disease responds better to etretinate or extracorporeal photochemotherapy. Localized cutaneous cGVHD may be treated with topical corticosteroids alone. Few reports on the effect of treatments in GVHD clearly describe the cutaneous involvement and the influence of the treatment on the skin. Therefore, dermatologists should be deeply involved in the diagnosis and treatment of GVHD, and good dermatologic grading systems should be developed. Theses changes will increase our knowledge of cutaneous GVHD, and relevant data in the evaluation of the effect of therapy in the disease will be obtained.     

Mycophenolate mofetil therapy for moderate to severe atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that can be refractory to topical and systemic corticosteroids, phototherapy, topical immunomodulators and systemic immunosuppressive drugs. Recent studies have shown promise for the use of mycophenolate mofetil (MMF) to treat recalcitrant AD. AIM: To assess the effectiveness and adverse effects of MMF used for moderate to severe AD in a university outpatient dermatology clinic. METHODS: A retrospective chart review of 20 patient charts was conducted for patient age, gender, duration of disease, prior therapies, concomitant therapy, clinical response and adverse side-effects. RESULTS: Of the 20 patients, 17 improved within 4 weeks of starting MMF therapy. Ten patients had disease remission and were subsequently able to discontinue MMF. Seven attained satisfactory control of their AD using MMF as maintenance therapy. Overall, MMF was well tolerated, with mild headaches, gastrointestinal complaints and fatigue as the commonest side-effects. During therapy, herpes zoster developed in four patients, Staphylococcus aureus cutaneous infections in two, and herpes simplex in one. One patient discontinued MMF because of insufficient control of pruritus. CONCLUSION: MMF can be rapidly effective and well tolerated in patients with moderate to severe AD resistant to conventional therapies. The limitations of this retrospective study include no control group and a lack of a standardized scoring index to assess improvement, and the concomitant use of adjuvant therapies makes the contribution of MMF alone difficult to assess. Larger controlled studies are needed.     

The changing face of graft-versus-host disease

Despite advances in the procedure and posttransplantation immunosuppressive therapy, more than half of allogeneic hematopoietic stem cell transplant (HSCT) recipients develop graft-versus-host disease (GVHD), which remains a major cause of morbidity and mortality. Modern HSCT protocols have resulted in substantial alterations in the timing and relative incidences of acute and chronic GVHD, making traditional classification schemes obsolete. This article reviews major changes in HSCT during the past decade, evolving concepts of acute and chronic GVHD (including new diagnostic criteria) and the expanding spectrum of cutaneous GVHD. It focuses on observations that have led to a better delineation of the full constellation of skin findings in chronic cutaneous GVHD, including lichen sclerosus, morpheaform lesions, and eosinophilic fasciitis. Recent insights into pathogenesis of GVHD, lessons from GVHD arising in settings outside HSCT, and therapeutic advances also are highlighted.     

An alternate-day corticosteroid regimen for pemphigus vulgaris. A 13-year prospective study

BACKGROUND: Pemphigus vulgaris (PV) at the early, usually oral and relatively stable stage, represents the majority of PV patients. Treatment modalities usually do not differ compared to those for the fully established disease. OBJECTIVES: To prospectively assess a standardized and effective therapeutic approach that aims at less morbidity due to adverse reactions. METHODS: The following regimen, also known as Lever's mini treatment (LMT), was used. Forty mg of oral prednisone on alternate days plus 100 mg azathioprine every day were administered until the complete healing of all lesions. A gradual monthly and later bimonthly decrease of prednisone was followed by the tapering of a second immunosuppressive agent, in a one-year period. RESULTS: Seventy-four patients suffering from early-stage-PV, and representing 70% of all PV patients seen through the years 1991-2003, were eligible in the study. Total follow-up period was 76 +/- 37 (26-180) months. During the 53 +/- 26 months of LMT, 6 (8%) patients dropped out of therapy, 9 (12%) required a change to another treatment, two (3%) died and 57 (77%) achieved a lesion-free condition. Forty-five (61%) patients were in complete remission for 27 +/- 29 months. Significant morbidity was estimated 4/74 (5.2%). Disease 'breakthroughs' necessitating treatment adjustments occurred in 30 patients, usually throughout the last phase of therapy and post-treatment follow-up. CONCLUSION: LMT may be a standardized therapeutic approach for the early and relatively stable stage of PV, resulting in high efficacy, safety and quality of life profile.     

Steroid sparing effect of intravenous immunoglobulin therapy in patients with pemphigus foliaceus

Pemphigus foliaceus (PF) is a rare autoimmune cutaneous blistering disease, with only skin involvement. Systemic corticosteroids and immunosuppressive agents are the mainstay of therapy. However, some patients develop multiple side effects to systemic corticosteroids, when they are used in high doses over prolonged periods. In some patients, immunosuppressive agents are not effective or contraindicated. In such patients, alternative treatment modalities are needed. The purpose of this study is to demonstrate the use of intravenous immunoglobulin (IVIg) therapy in seven patients with severe PF, who were steroid-dependent. The following information was recorded in each patient, before and after IVIg therapy initiation: total dose and total duration of prednisone therapy, and number of relapses. In addition, the highest dose and side effects of prednisone therapy, and duration of observation were documented. After the initiation of IVIg treatment, doses of systemic corticosteroids were gradually reduced and eventually discontinued over a mean period of 2.8 months. Thereafter, IVIg was used as monotherapy. A statistically significant difference was noted between pre-IVIg therapy and after the initiation of IVIg therapy in the total dose (p = 0.005), and total duration of prednisone treatment (p = 0.02), and the number of relapses (p = 0.002). In all seven patients, IVIg produced an effective clinical response and demonstrated a steroid-sparing effect. In patients with PF, who are steroid-dependent and in whom use of conventional immunosuppressive agents is contraindicated, IVIg appears a safe and effective agent to induce and maintain a prolonged clinical remission.     

Tacrolimus ointment in the treatment of chronic cutaneous graft-vs-host disease: a case series of 18 patients

BACKGROUND: Tacrolimus (formerly FK 506) is an immunosuppressive drug that works by inhibiting calcineurin, a calcium-dependent protein phosphatase required for immune function. Tacrolimus has been shown to be effective topically in atopic dermatitis and systemically in psoriasis and graft-vs-host disease (GVHD). However, its efficacy in treating cutaneous GVHD when applied topically has not been reported. OBJECTIVE: To assess the therapeutic efficacy of 0.1% tacrolimus ointment on chronic cutaneous GVHD in patients with symptoms refractory to systemic corticosteroid therapy. RESULTS: Tacrolimus ointment effectively treated pruritus and/or erythema in 13 (72%) of 18 patients with chronic GVHD. Responding patients had a rapid effect within several hours to days. Effectiveness was measured by means of patient report, results of physical examination, side-by-side comparisons of tacrolimus vs a vehicle control, and temporal flares of the cutaneous symptoms of the disease in the context of stopping tacrolimus ointment therapy. Because of the progression of GVHD and in 2 cases, loss of drug efficacy, all patients eventually went on to receive more aggressive treatment, including increases in steroid dosage, psoralen-UV-A therapy, and extracorporeal photopheresis. CONCLUSIONS: This case series suggests that tacrolimus ointment has efficacy in treating the erythema and pruritus of steroid-refractory, chronic cutaneous GVHD in most patients. The rapid response of tacrolimus ointment may provide a useful therapeutic bridge to systemic therapies that have slower onset, such as psoralen-UV-A therapy or extracorporeal photopheresis.     

Combination antimalarials in the treatment of cutaneous dermatomyositis: a retrospective study

OBJECTIVE: To observe whether the use of antimalarials in combination resulted in significant improvement in the cutaneous signs and symptoms of patients with dermatomyositis who did not otherwise respond to the use of single-agent antimalarial therapy. DESIGN: Retrospective case series of 17 patients treated between January 1, 1991, and December 31, 2002. SETTING: An ambulatory medical dermatology clinic in an academic center.Patients Patients had adult-onset dermatomyositis with predominantly cutaneous symptoms and a follow-up period at our clinic of at least 6 months. Cases in which it was not possible to assess the effect of treatment on cutaneous symptoms were not included.Intervention Treatment regimens varied and included the use of antimalarials, prednisone, methotrexate, and other medications. MAIN OUTCOME MEASURES: Physician-observed and patient-reported improvement based on erythema, pruritus, and extent of affected skin. RESULTS: Seven of 17 patients experienced at least near clearance in cutaneous symptoms with the use of antimalarial therapy alone: 4 of these patients required combination therapy (hydroxychloroquine sulfate-quinacrine hydrochloride or chloroquine phosphate-quinacrine), while 3 of them responded well to antimalarial monotherapy. The median time required to reach the response milestones on the final working therapeutic regimen was 3 months (mean, 4.8 months; range, 2-14 months). Six patients did not respond significantly to any type of therapy, including nonantimalarials. CONCLUSION: Our experience suggests that a significant subgroup of patients whose skin lesions have been unresponsive to a single antimalarial benefit from combination therapy with hydroxychloroquine and quinacrine or chloroquine and quinacrine, but controlled clinical trials are warranted to assess the extent of benefit.     

Cutaneous involvement of dermatomyositis can respond to Dapsone therapy

BACKGROUND: Dapsone (4,4-diaminodiphenylsulfone) is a sulfone antibiotic used in the treatment of leprosy, but dermatologists more commonly utilize its anti-inflammatory properties particularly directed against leukocytes to treat various bullous disorders, erythema nodosum, pyoderma gangrenosum, Sweet's syndrome, cutaneous vasculitis, and cutaneous forms of lupus erythematosus. The cutaneous manifestations of dermatomyositis are often resistant to antimalarial and immunosuppressive therapies. METHODS: Two patients with cutaneous dermatomyositis unresponsive to combination therapy with prednisone, hydroxychloroquine, quinacrine, and immunosuppressive medications had Dapsone added to their therapy. RESULTS: Both patients showed rapid improvement with the addition of Dapsone. Each had an exacerbation of their cutaneous dermatomyositis on Dapsone with withdrawal and subsequent improvement when the Dapsone was reinstituted. CONCLUSIONS: Dapsone therapy for cutaneous dermatomyositis may have a wider role in treatment for these patients refractory to prednisone and antimalarial therapy.     

Topical nitrogen mustard therapy in patients with Langerhans cell histiocytosis

Background Langerhans cell histiocytosis (LCH) is characterized by abnormal proliferation and infiltration of Langerhans cells in different organs. The skin is frequently involved either as unisystem or multisystem disease. Objectives To review the clinical response and side‐effects of nitrogen mustard therapy in LCH in children and adults with unisystem or multisystem disease. Patients and methods This retrospective study includes 10 children and four adults with LCH, treated with nitrogen mustard from 1975 to 2010. The median extent of skin involvement was 46% (range 5–100%). Results Overall, 13 patients had complete or partial response. Although eight patients achieved a complete response with a median time of 12·3 months (range 36 days to 1·9 years), six of these patients ultimately relapsed. One patient, who had unisystem disease limited to the skin, initially showed progression of her cutaneous lesions with nitrogen mustard treatment. Although subsequently the cutaneous lesions completely regressed, concomitant systemic involvement was noted. Four other patients similarly experienced improvement of their skin lesions with treatment, but also exhibited progression of the LCH systemically. The patients were treated with other therapies prior and adjunctive to nitrogen mustard. However, five patients had progression to other organs, despite regression of skin lesions, which supports that the treatment effect in the skin is related to topical nitrogen mustard. Six patients developed contact dermatitis to nitrogen mustard. Conclusions Topical nitrogen mustard can be an effective and safe therapy in both children and adults with cutaneous LCH, although relapses are common.     

Long-term extracorporeal photoimmunotherapy for treatment of chronic cutaneous graft-versus-host disease: observations in four patients.

BACKGROUND: Chronic cutaneous graft-versus-host disease (GvHD) can arise as a late complication after allogeneic bone marrow transplantation. Patients with extensive disease to date require intensive early and long-term immunosuppression; however, treatment is often insufficient. Since the beneficial effects of phototherapy for chronic cutaneous GvHD are well known, extracorporeal photoimmunotherapy (ECP) was also tried with some success for a few single patients with this disease. OBJECTIVE: The long-term effect of ECP was evaluated in 4 patients with therapy-resistant severe chronic cutaneous GvHD after allogeneic bone marrow transplantation. METHODS: Four patients were treated with monthly sessions of ECP over a period of 16-40 months. Disease severity was assessed by a semiquantitative score adapted from the literature including extent of skin area involved, rigidity of the skin, involvement of joints and immunosuppressive drug consumption. RESULTS: In all patients, a favorable response was observed after 6-12 treatment cycles. One patient had a complete response, 2 patients had a partial response, and 1 patient had a minor response after treatment. In 2 patients, immunosuppressive medication started before initiating ECP could be reduced or completely withdrawn under ECP. Peripheral blood lymphocyte immunophenotyping revealed reduction of CD3+ CD4+ T cells in 3 patients and of elevated CD3+ CD8+ and CD57+ CD8+ T cell subsets in 2 patients. Conclusion: ECP is effective in treating severe chronic cutaneous GvHD. ECP possibly exerts its effects by reducing the number of CD8+ suppressor/cytotoxic T cells, the presumptive effector cells of GvHD. ECP is well tolerated with essentially no side effects and allows reducing the dosage of immunosuppressive agents.