Dry eye disease and risk factors for corneal complications in chronic ocular graft-versus-host disease

Purpose: The current study was carried out to evaluate the clinical features and management outcomes of dry eye disease (DED) in chronic ocular GvHD following allogenic hematopoietic stem cell transplantation (HSCT). Methods: A retrospective review of consecutive patients diagnosed with chronic ocular GvHD between 2011 and 2020 was performed at a tertiary eye care network. Multi?variate regression analysis was carried out for identifying risk factors associated with progressive disease. Results: A total of 34 patients (68 eyes) with a median age of 33 years [inter?quartile range (IQR) 23–40.5] were studied. The most common indication for HSCT was acute lymphocytic leukemia (26%). Ocular GvHD developed at a median of 2 years (IQR 1–5.5 years) after HSCT. Aqueous tear deficiency was present in 71% of the eyes, of which 84% had a Schirmer value of <5 mm. The median visual acuity at presentation and that after a median follow? up of 6.9 months were comparable at 0.1 log minimum angle of resolution (logMAR) (P = 0.97). Topical immunosuppression was required in 88% of cases, and with this, improvement in corneal (53%, P = 0.003) and conjunctival staining scores (45%, P = 0.43) was noted. A progressive disease was present in 32% with persistent epithelial defects being the most common complication. Grade 2 conjunctival hyperemia [odds ratio (OR): 2.6; P = 0.01] and Schirmer’s value <5 mm (OR: 2.7; P = 0.03) were found to be associated with progressive disease. Conclusion: Aqueous deficient DED is the most common ocular manifestation of chronic ocular GvHD, and the risk of the disease progression is greater in eyes with conjunctival hyperemia and severe aqueous deficiency. Awareness among ophthalmologists of this entity is essential for its timely detection and optimal management.

Extensive Fasciitis in Sclerotic-type Chronic Cutaneous Graft-versus-Host Disease / 대한피부과학회지

Fasciitis can occur very rarely with sclerotic-type chronic cutaneous graft-versus-host disease (GVHD). A 54-year-old woman presented with painful skin tightness on upper and lower limb with limited range of movement. She was diagnosed with chronic myelocytic leukemia 5 years ago and underwent allogeneic bone marrow transplantation. Histopathologically, the interlobular septum of subcutis and fascia were remarkably thickened with fibrosis and moderate inflammatory infiltrates accompanying the dilated lymphatic channels with considerable leakage of lymph fluids. Herein, we report a case of extensive fasciitis as a manifestation of chronic GVHD associated with poor prognosis.

High Frequency of Male Microchimerism in Peripheral Blood Mononuclear Cells of Korean Women with Scleroderma, Resembling Skin Manifestations of Chronic Graft Versus Host Disease / 임상소아혈액종양

BACKGROUND: Bidirectional traffic of cells at the feto-maternal interface has been shown during pregnancy and fetal cells have been found to persist in maternal peripheral blood for decades after childbirth. Fetal-microchimerism has been reported in women with scleroderma, which shares a number of characteristics with chronic graft versus host disease (GVHD), although its contribution to the disease pathogenesis remains unclear. We performed this study to determine the frequency of male microchimerism in peripheral blood of patients with scleroderma or normal healthy women with son.METHODS: PCR targeting the Y chromosome specific DYZ1 sequence was employed to test DNA extracted from peripheral blood mononuclear cells of 26 women with scleroderma and 10 healthy women who had given birth to at least one son.RESULTS: Male DNA was detected in 16 of 26 (61.5%) women with scleroderma. Whereas male DNA was not detected in any healthy women who had given birth to son.CONCLUSION: Although fetal microchimerism in women with scleroderma was documented, additional studies will be necessary to determine whether microchimerism plays a role in the pathogenesis of this or other autoimmune disease.

Prognostic Implications of the NIH Consensus Criteria in Children with Chronic Graft-versus-Host Disease

PURPOSE: In this study, we analyzed a cohort of children with chronic graft-versus-host disease (GvHD) according to the NIH consensus classification (NCC) in order to observe whether global assessment at diagnosis correlates with GvHD-specific endpoints. We then studied the clinical course of these patients, specifically with regards to episodes of GvHD exacerbation requiring treatment escalation. MATERIALS AND METHODS: Recipients of either allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) from January 2006 to August 2008 at the Department of Pediatrics, The Catholic University of Korea were evaluated for chronic GvHD, which was diagnosed according to the NCC. The course of chronic GvHD in these patients was then followed. RESULTS: Of 59 evaluable patients, 23 developed chronic GvHD for a cumulative incidence of 39.3%. Upon multivariate analysis, previous acute GvHD (> or =grade II) had a significant impact on chronic GvHD incidence. With a median duration of systemic treatment for chronic GvHD of 501 days, no significant relationship was found between initial global severity of chronic GvHD and either duration of immunosuppressive treatment or final clinical response to treatment. Fifteen patients (65%) experienced at least one episode of chronic GvHD exacerbation during the period of follow-up, with a median of four exacerbations in the subgroup of patients who experienced such events. Lung GvHD resulted in the highest number of exacerbations per diagnosed patient, followed by oral GvHD. CONCLUSION: Analysis of this small cohort indicates that global assessment as proposed by the NCC may have limited correlations with GvHD-specific endpoints, possibly due to the favorable response of children to treatment.

High Frequency of Male Microchimerism in Peripheral Blood Mononuclear Cells of Korean Women with Scleroderma, Resembling Skin Manifestations of Chronic Graft Versus Host Disease / 임상소아혈액종양

BACKGROUND: Bidirectional traffic of cells at the feto-maternal interface has been shown during pregnancy and fetal cells have been found to persist in maternal peripheral blood for decades after childbirth. Fetal-microchimerism has been reported in women with scleroderma, which shares a number of characteristics with chronic graft versus host disease (GVHD), although its contribution to the disease pathogenesis remains unclear. We performed this study to determine the frequency of male microchimerism in peripheral blood of patients with scleroderma or normal healthy women with son. METHODS: PCR targeting the Y chromosome specific DYZ1 sequence was employed to test DNA extracted from peripheral blood mononuclear cells of 26 women with scleroderma and 10 healthy women who had given birth to at least one son. RESULTS: Male DNA was detected in 16 of 26 (61.5%) women with scleroderma. Whereas male DNA was not detected in any healthy women who had given birth to son. CONCLUSION: Although fetal microchimerism in women with scleroderma was documented, additional studies will be necessary to determine whether microchimerism plays a role in the pathogenesis of this or other autoimmune disease.

Vesicles in Chronic Graft-versus-host Disease / 대한피부과학회지

Chronic graft-versus-host disease (GVHD) usually presents 100 days after allogenic bone marrow transplantation. Chronic GVHD cutaneous lesions are characterized by lichenoid or sclerodermoid variants. Vesicles, a common presentation in patients with acute GVHD, rarely appear in chronic GVHD. We report a case of a 49-year-old man who presented with bilateral vesicles on lower extremities. He was diagnosed with myelodysplastic syndrome 2 years before and was taking oral cyclosporine after the allogenic bone marrow transplantation. Six months post-transplantation, lichenoid and sclerodermoid lesions developed on his entire body and he was diagnosed with chronic GVHD and eosinophilic fasciitis. A biopsy of the vesicles revealed detached lower margins of the epidermis, necrotized keratinocytes, and infiltration of lymphocytic inflammatory cells. Administration of oral prednisolone alleviated the patient's symptoms. This is an interesting case showing a new pattern of vesicle appearance after development of typical chronic GVHD lesions.

The Strategies for the Prevention of Chronic GVHD in Hematopoietic Stem Cell Transplantation

Chronic graft-versus-host disease (GVHD) is the most frequent late complication after hematopoietic cell transplantation and has a major impact on the quality of life and survival. As the pathophysiology of GVHD is still incompletely understood, it has been difficult to design effective prophylactic regimens. However, prevention of acute GVHD appears to result in a lower incidence of chronic GVHD. The use of younger, non-allo-sensitized donors, preferentially of the same sex as the patient, and the use of stem cells other than G-CSF-mobilized peripheral blood stem cells, are associated with a decreased frequency of chronic GVHD. Further, the incorporation of thymoglobulin into the conditioning regimen has been demonstrated as beneficial to reduce chronic GVHD and delayed complications.

A Case of Simultaneous Occurrence of Vitiligo-like and Morphea-like Lesion in Recipient of Allogenic Bone Marrow Transplantation / 대한피부과학회지

Vitiligo and morphea are two distinct entities of unknown etiology, although their existence implies that the immune system and/or the central or peripheral nervous system has been incriminated. Only a few reports of their simultaneous occurrence are on record. Here we report a case of a 39 year old woman affected with both vitiligo of the face, chest and hand and morphea of shoulder and trunk. Since the two diseases appeared after bone marrow transplantation, if could be deduced that there is a possible association between them. Two diseases observed simultaneously in this patient may be derived from the common pathomechanism. An autoimmune etiology is thought to play a part in both of these diseases.

Graft-versus-Host Disease: Report of Four Cases

No abstract available.