Comedonal graft‐vs‐host disease: a distinct clinical expression of a lichenoid follicular GVHD

We report two cases of chronic follicular graft‐vs‐host disease (GVHD) that resemble closed and open acne‐like comedones. We propose the term ‘comedonal GVHD’ for this variant. A 47‐year‐old man presented with multiple 2–4‐mm acne‐like follicular papules in facial areas on day 82 status post bone marrow transplantation. A biopsy showed follicular infundibular dilation with keratotic plugs, hypergranulosis and vacuolar alteration (hydropic degeneration) of the basal layer, with dyskeratotic (apoptotic) keratinocytes, scattered lymphocytes and vascular ectasia of the superficial dermal plexus. We diagnosed chronic follicular lichenoid GVHD. The second patient was a 53‐year‐old female. On day 420 after transplantation, she presented with generalized dark to grayish, confluent, indurated lesions with confluent papules and unevenly distributed comedo‐like lesions. Skin biopsy showed sclerotic dermis and also dilated follicular infundibula with keratotic plugging, hypergranulosis and vacuolar alteration (hydropic degeneration) of the basal layer of the epidermis. We established the diagnosis of chronic sclerodermoid GVHD with follicular lichenoid involvement. The presence of open and closed comedones on the trunk and facial region of an adult raises several differential diagnosis but in our patients, histopathologic study demonstrated typical features of GVHD, which led to this diagnoses despite the peculiar clinical findings.     

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.     

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.     

Acute follicular graft-versus-host disease.

We documented by clinical, histopathologic and immunohistochemical analysis a case of acute follicular graft-versus-host disease (GVHD), in which an erythematous-to-violaceous follicular papular eruption constituted the major clinical pattern of cutaneous involvement. Although acute follicular GVHD is rare, it is important to recognize it as an early skin manifestation of acute cutaneous GVHD allowing prompt therapy.     

Lichen sclerosus and eosinophilic fasciitis as manifestations of chronic graft-versus-host disease: expanding the sclerodermoid spectrum

Chronic cutaneous graft-versus-host disease (GVHD) is classically divided into two major clinical categories--lichenoid and sclerodermoid. Although diffuse areas of sclerosis as in scleroderma characterize the more advanced stages of the sclerodermoid form, the initial circumscribed plaques would be more correctly described as morpheaform. Eosinophilic fasciitis (EF) (a fibrosing disorder related to deep morphea) and lichen sclerosus (LS) have also been reported as manifestations of sclerodermoid GVHD. However, these two presentations of GVHD have not been emphasized in the dermatologic literature. We describe 6 patients, all of whom developed LS and two of whom also developed EF in the context of chronic GVHD. Each patient presented clinically with hypopigmented plaques that exhibited wrinkling, scaling, and follicular plugging. These lesions demonstrated the classic histologic features of LS including epidermal atrophy; a subepidermal zone of pale-staining, homogenized collagen; and a bandlike lymphocytic infiltrate. Although all patients eventually developed morpheaform and/or sclerodermoid GVHD, LS was a prominent part of the initial presentation of chronic cutaneous GVHD in every case. The LS lesions tended to occur on the neck and upper to mid aspect of the trunk, whereas morpheaform lesions favored the lower aspect of the trunk. EF involved the extremities (sparing the hands and feet), and was characterized clinically by an acute onset of pain and edema followed by induration with a rippled appearance. This case series serves to expand the spectrum of sclerodermoid GVHD, with LS as the most superficial and EF as its deepest manifestation.     

Atypical acute graft-versus-host disease

Acute graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic bone marrow transplantation. It is important to recognize the dermatologic manifestations of acute GVHD, as skin is often the initial organ of involvement. We present a case of acute GVHD characterized by rare clinical and histopathologic findings as only two erythematous nodules clinically and abrupt follicular wall necrosis histopathologically.     

Cutaneous manifestations of chronic graft-versus-host disease

Graft-versus-host disease (GVHD) occurs in a number of clinical settings. It is well recognized after bone marrow transplantation, an increasingly used therapeutic option for haematologicl disorders. Chronic GVHD, occurring at an interval greater than 100 days post-transplant, has many systemic manifestations, but it is the cutaneous manifestations which are most frequent and often most troubling to the patient In this review article, the wide spectrum of cutaneous chronic GVHD (including involvement of hair, nails and mucosae), and its complications and associations are discussed. The clinical and histological features and management guidelines are presented to assist the dermatologist with diagnosis and treatment of this condition.     

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.     

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.     

A Case of Chronic GVHD Following Bone Marrow Transplantation from a Phenotypically HLA-Matched Unrelated Donor

A 45-year-old male with chronic myelocytic leukemia who received a bone marrow transplantation from a phenotypically HLA-matched unrelated donor developed chronic GVHD on day 100 post transplantation. He developed a slight fever, malaise, hepatic dysfunction and extensive itchy erythema with scaling over his entire body. The inflammatory skin lesion developed into erythroderma in about two weeks. H&E staining of a skin biopsy revealed eosinophilic bodies and a lymphocytic infiltration in the dermis and epidermis, which were compatible with the early phases of chronic GVHD. Immunohistochemistry revealed that keratinocytes expressed dense HLA-DR and ICAM-1 epitopes. Langerhans cells (CD1a⁺ cells) had disappeared from the epidermis. Many T cells (CD3⁺ cells) had migrated into the epidermis as well as into the reticular dermis. The majority of the T cells in the epidermis were CD8⁺ cells, while almost all the T cells in the dermis were CD4⁺ cells. These immunohistochemical features were similar to those previously reported for acute cutaneous GVHD. Despite the corticosteroid therapy, the eruptions did not disappear. The patient was then treated with whole body bath-methoxsalen (Oxsoralen®) plus ultraviolet A (UVA). The bath-psoralen plus UVA therapy was effective in this patient.     

Fotoféresis extracorpórea en enfermedad injerto contra huésped en una población pediátrica

BackgroundExtracorporeal photopheresis (ECP) is an immunomodulatory therapy used to treat graft-vs-host disease (GVHD) in adults and children. Few studies have examined its use in children.ObjectiveTo describe demographic characteristics, clinical response, adverse effects, and outcomes in a series of pediatric patients with acute or chronic GVHD treated with ECP.Material and methodsWe included all pediatric patients with acute or chronic GVHD treated with ECP by the Dermatology Department of Hospital Italiano de Buenos Aires between January 2012 and December 2018. We used the UVAR-XTS™ system (2 patients) and the CELLEX system (7 patients). Patients with acute GVHD received 2 sessions a week and were reassessed at 1 month, while those with chronic GVHD received 2 sessions every 2 weeks and were reassessed at 3 months. Treatment duration in both scenarios varied according to response.ResultsWe evaluated 9 pediatric patients with corticosteroid-refractory, -dependent, and/or -resistant GVHD treated with ECP. Seven responded to treatment and 2 did not. Response was complete in 1 of the 9 patients with skin involvement and partial in 7. Complete response rates for the other sites of involvement were 60% (3/5) for the liver, 50% (1/2) for the gastrointestinal system, and 80% (4/5) for mucous membranes. Two patients died during the study period.ConclusionECP is a good treatment option for pediatric patients with acute or chronic GVHD.     

Expression of CCR5 in graft-versus-host disease (GVHD) of the skin: immunohistochemical staining of 38 cases

To ascertain the involvement of CCR5 in prolongation of graft-versus-host disease (GVHD), we performed immunohistochemical staining of CCR5 in 38 GVHD samples (23 acute and 15 chronic). A total of seven out of 15 cases of chronic GVHD were positive for CCR5; however, only two out of 23 in acute GVHD were positive for CCR5. In three cases, expression of CCR5 in infiltrating lymphocytes was negative in the acute phase, but positive in the chronic phase of GVHD. These findings suggest that the immunopathological mechanism that differentiates between acute and chronic GVHD is a CCR5-mediated immunoreaction.     

Follicular granular parakeratosis

An 83-year-old patient presented herself with a ten-year history of keratotic papules on her trunk. A biopsy of this process revealed granular parakeratosis confined to the infundibulum of a follicle. Exclusive follicular involvement in granular parakeratosis has not been previously described.     

Analysis of risk factors for acute cutaneous graft-versus-host disease after allogeneic stem cell transplantation

BACKGROUND: Although skin is typically the first site of involvement of acute graft-versus-host disease (GVHD), most standard recommended staging and grading criteria allow enrolment of patients with involvement of GVHD target organs other than the skin in studies analysing risk factors for acute GVHD after stem cell transplantation (SCT). OBJECTIVES: To determine the risk factors for developing histologically confirmed acute cutaneous GVHD in patients who underwent allogeneic SCT for different haematological disorders. METHODS: This retrospective study was based on review of clinical files and databases from 300 consecutive patients with several haematological disorders who received allogeneic SCT between 1 January 1984 and 31 December 1999 at Hospital Universitario de la Princesa, Madrid, Spain. Variables evaluated included diagnosis of haematological disorder, age and gender (donor and recipient), HLA matching, female donor to male recipient, donor and recipient viral serology (cytomegalovirus), conditioning regimen, GVHD prophylaxis, blood counts at day of engraftment, mortality, cause of death, and survival at 100 days, 5 years and 10 years following SCT. RESULTS: In multivariate analysis, risk factors for acute cutaneous GVHD were type of haematological disease (P = 0.006), HLA disparity (P = 0.006), number of transplants per patient (P = 0.017), conditioning regimen (P = 0.001), and GVHD prophylaxis (P = 0.025). Survival rates did not differ significantly for cases and controls. CONCLUSIONS: Risk factors for acute cutaneous GVHD were a diagnosis of chronic myeloid leukaemia, HLA disparity, receipt of more than one SCT, conditioning regimens including total body irradiation, and GVHD prophylaxis regimens other than ciclosporin plus methotrexate. Other common risk factors for acute GVHD without specific target organ involvement showed no significant association with the risk for developing acute GVHD affecting the skin as primary target organ.     

Dyskeratosis congenita in a girl simulating chronic graft-vs-host disease

Dyskeratosis congenita (DCG) is a rare genodermatosis characterized primarily by reticular hyperpigmentation of the skin, dystrophy of the nails, and leukoplakia. It is frequently associated with Fanconi-type pancytopenia. Although DCG has a male predisposition, it has been reported in several female patients. We encountered a case of DCG occurring in a girl whose clinical features simulated chronic graft-vs-host disease (GVHD). Because DCG and chronic GVHD share several clinical and histologic features, physicians should always examine a patient for possible DCG whenever a diagnosis of chronic GVHD is considered. In addition, the similar manifestations of the two disorders suggest a similar pathogenesis on a cellular level in the immunologic system.     

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.     

A Case of Generalized Lichen Sclerosus et Atrophicus

A 62-year-old female, with previous history of asthma and hypertension, presented with generalized hyperpigmented skin lesion, found a year ago. Physical examination revealed brown colored lichenified and sclerotic patches on the lower abdomen and flexural areas of extremities. Punch biopsy was performed and histopathological examination revealed hyperkeratosis, follicular plugging and thinning in epidermis. In dermoepidermal junction, cleft like space separating atrophic epidermis and dermis was seen. Also, lichenoid lymphocytic infiltration was observed in mid-dermis. Based on clinical and histopathological findings, a diagnosis of generlaized lichen sclerosus et atrophicus (LSA) was made. Other laboratory examinations were unremarkable. As there is no standard treatment for LSA, the patient received various treatments including topical steroid, tacrolimus and narrow-band ultraviolet B therapy. The skin lesion has softened and its color improved after treatment. LSA is defined as infrequent chronic inflammatory dermatosis with anogenital and extragenital manifestations. Generalized type is rare and genital involvement is the most frequent and often the only site of involvement. We report this case as it is an uncommon type of LSA with generalized hyperpigmented and sclerotic skin lesion in a postmenopausal female patient.     

Chronic cutaneous graft-versus-host disease simulating hypertrophic lupus erythematosus--a case report of a new morphologic variant of graft-versus-host disease

The spectrum of clinical and histopathologic features associated with chronic graft-versus-host disease (GVHD) is broad, with recognized variants simulating scleroderma, lichen sclerosus, eosinophilic fasciitis, and de novo diffuse melanoderma. We report a case of a patient with multiple myeloma who presented approximately 1 year after his allogeneic hematopoietic stem cell transplantation with lesions of chronic lichenoid GVHD that harbored features of hypertrophic lupus erythematosus (LE) and that was initially mistaken for a superficial well-differentiated squamous cell carcinoma (SCC). However, in 4 years of follow-up, the patient failed to develop any evidence of cutaneous or systemic LE, actinic damage, or SCC, and the lesions cleared with topical and systemic treatments appropriate for chronic GVHD. For proper interpretation of the histologic findings of GVHD, it is important for the dermatopathologist to be aware of unusual manifestations. Knowledge of the occurrence of hypertrophic LE and familiarity with its histologic features is also important to avoid an erroneous diagnosis of SCC in immunosuppressed patients.     

A case of sclerodermatous graft-versus-host disease following autologous peripheral blood stem cell transplantation

We report a 65-year-old woman with chronic graft-versus-host disease (GVHD) who developed severely sclerotic skin on the fingers, hand and trunk following autologous peripheral blood stem cell transplantation (APBSCT). The patient had suffered from breast cancer and been treated with surgery and chemotherapy. She showed pancytopenia and was treated with APBCST. Four years after APBSCT, she developed the severe sclerotic changes on the fingers, hands, extremities and trunk. The skin biopsy showed a flattened epidermis and a proliferation of collagen bundles in the dermis. No anti-nucleolar DNA titers were detected in the serum. She was diagnosed with chronic GVHD. Despite treatment with oral prednisolone, the skin sclerotic change developed and the breast cancer recurred. She died due to pericarditis. This is a rare case of sclerodermatous GVHD following APBSCT. The serum interleukin (IL)-12 levels were examined during the treatment.