Coffee Fruit Rot: The Previously Unrecognized Role of Fusarium and Its Interactions with the Coffee Berry Borer (Hypothenemus hampei).

Coffee fruit rot (CFR) is a well-known disease worldwide, mainly caused by Colletotrichum spp., the most important species being C. kahawae subsp. kahawae. In Puerto Rico, Colletotrichum spp. were identified as pathogens of coffee fruits. The coffee berry borer (CBB) was shown to be a dispersal agent of these fungi, and interaction of Fusarium with Colletotrichum affecting coffee fruits was suggested. In this study, we demonstrated that Fusarium spp. also cause CFR in Puerto Rico. Fusarium spp. are part of the CBB mycobiota, and this insect is responsible for spreading the pathogens in coffee fields. We identified nine Fusarium spp. (F. nirenbergiae, F. bostrycoides, F. crassum, F. hengyangense, F. solani-melongenae, F. pseudocircinatum, F. meridionale, F. concolor, and F. lateritium) belonging to six Fusarium species complexes isolated from CBBs and from rotten coffee fruits. Pathogenicity tests showed that F. bostrycoides, F. lateritium, F. nirenbergiae, F. solani-melongenae, and F. pseudocircinatum were pathogens causing CFR on green coffee fruits. F. bostrycoides was the predominant species isolated from the CBB mycobiota and coffee fruits with symptoms of CFR, suggesting a close relationship between F. bostrycoides and the CBB. To our knowledge, this is the first report of F. bostrycoides, F. solani-melongenae, F. pseudocircinatum, and F. nirenbergiae causing CFR worldwide and the first report of F. lateritium causing CFR in Puerto Rico. Understanding the CFR disease complex and how the CBB contributes to dispersing different Fusarium spp. on coffee farms is important to implement disease management practices in Puerto Rico and in other coffee-producing countries.

Long-term extracorporeal photochemotherapy in a pediatric patient with refractory sclerodermatous chronic graft-versus-host disease.

Sclerodermatous chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT) in children is difficult to treat and life-threatening. Extracorporeal photochemotherapy (ECP; photopheresis), an immunomodulatory therapy that involves the infusion of autologous peripheral blood leukocytes after ex vivo exposure to the photoactive agent 8-methoxypsoralen and ultraviolet A radiation, is an effective treatment for steroid-refractory cGVHD. After undergoing allogeneic HSCT for pre-B-cell acute lymphoblastic leukemia, a 14-year-old boy developed extensive sclerodermatous cGVHD that was refractory to prednisone, tacrolimus, and sirolimus. ECP was administered over the course of 53 months, during which the skin softened substantially and immunosuppressive therapy was discontinued. This case suggests that long-term ECP is a viable option in children with sclerodermatous cGVHD.

Extracorporeal photochemotherapy for the treatment of refractory Crohn's disease.

Crohn's disease is an idiopathic, relapsing inflammatory disorder of the gastrointestinal tract. We prospectively evaluated the use of extracorporeal photochemotherapy (ECP; photopheresis), an immunomodulatory therapy, to treat moderate or severe Crohn's disease (Crohn's Disease Activity Index [CDAI] score > or = 220 points) in 2 patients who failed multiple treatments, including immunosuppressants and anti-tumor necrosis factor agents. After at least 24 weeks of ECP with stable concomitant therapy, the patient with moderate disease achieved a clinical response (a decrease in CDAI score from baseline of > or = 100 points and an endpoint CDAI score of < or = 150 points), whereas the other patient with severe disease demonstrated limited improvement. ECP was well tolerated in both patients. These observations suggest that adjunctive ECP can be of benefit among patients with active, refractory Crohn's disease of moderate intensity. Further investigation is needed to define the role of ECP in treating Crohn's disease.

Treatment of extensive chronic graft-versus-host disease with extracorporeal photochemotherapy.

Extracorporeal photochemotherapy (ECP; photopheresis), an immunomodulatory therapy developed for cutaneous T-cell lymphoma, has shown promise in treating chronic graft-versus-host disease (cGvHD) in uncontrolled studies. The purpose of this study was to further examine the effects of ECP on cGvHD. ECP (administered initially 3 times weekly on alternating days) was retrospectively evaluated in 14 patients with extensive cGvHD following allogeneic hematopoietic stem cell transplantation. The median time from transplantation to ECP initiation was 29 months (range, 5-96 months). The median number of concomitant baseline treatments per patient was 3 (range, 0-5). During a median ECP duration of 17 months (range, 3-44 months), 3 patients (21%) achieved a complete cutaneous response (100% improvement), 4 patients (29%) achieved a partial cutaneous response (> or =50% improvement), and 7 patients (50%) had stable skin disease. The median time to response was 6 months (range, 2-15 months), and the median response duration was 5 months (range, 1-31 months). At endpoint, responses were ongoing in 4 patients. Resolution or improvement was noted in arthralgia (5/7 patients), oral changes (3/7), elevated liver enzymes (3/5), dry eyes (2/5), joint stiffness (3/3), pulmonary disease (1/3), and thrombocytopenia (1/1). Because of a favorable response, 11 of 13 patients (85%) who received prednisone at baseline were able to taper (7/13; 54%) or discontinue (4/13; 31%) this medication, and 12 of 14 patients (86%) were able to taper (11/14; 79%) or discontinue (1/14; 7%) ECP. Five-year posttransplantation survival was 77%. Our results suggest that adjunctive ECP improves cutaneous and extracutaneous manifestations of cGvHD and has a steroid-sparing effect.

Giant congenital melanocytic nevus with a large ulceration at birth: a 5-year follow-up.

Giant congenital melanocytic nevus (GCMN) is a rare birthmark that places patients at an increased lifetime risk of malignant melanoma. Herein, we describe an unusual case of GCMN that was followed up from birth until 5 years of age. A white girl was born, after an uncomplicated gestation, with a large cutaneous ulceration that extended over her entire back and laterally toward the anterior aspect of her trunk to involve the chest symmetrically. Biopsy specimens from several sites indicated GCMN that was centrally ulcerated. The patient was followed up closely, and the denuded area of skin was allowed to heal by secondary intention. By 19 months of age, the ulceration had healed completely. By 5 years of age, the nevus had lightened significantly and the scar tissue within the nevus had softened. The patient developed normally, meeting all milestones. Clinical and histologic examination did not reveal any signs of malignant transformation. The case we describe here delineates an approach to the long-term management of GCMN complicated by a large ulceration.

Photopheresis. Therapeutic potential in preventing restenosis after percutaneous transluminal coronary angioplasty.

Photopheresis (extracorporeal photochemotherapy) is an immunomodulatory therapy that entails the reinfusion of peripheral blood mononuclear cells after exposure to the photoreactive agent methoxsalen and ultraviolet A (UVA) radiation. Currently available at approximately 150 treatment centers worldwide, photopheresis is approved by the US FDA for advanced-stage cutaneous T-cell lymphoma (CTCL) and has also shown promise in treating nonmalignant immune-related conditions such as organ transplant rejection, acute and chronic graft-versus-host disease, and autoimmune disorders. The precise mechanism by which photopheresis evokes clinical responses is unknown, although this modality seems capable of modulating T-cell and monocyte activity. Clinical and laboratory findings suggest that the reinfusion of peripheral blood mononuclear cells after exposure to UVA-activated methoxsalen engenders an immune response against proliferating T-cell clones. Methoxsalen is a naturally occurring furocoumarin that is biologically inert until exposed to UVA radiation at the proper wavelength, at which time it irreversibly cross-links DNA thymine bases and arrests cell proliferation. T cells isolated from the peripheral blood of patients after photopheresis demonstrate significantly increased levels of apoptosis, whereas macrophages and dendritic cells exhibit the ability to phagocytize the apoptotic T cells. It is surmised that photopheresis enhances the uptake, processing, and presentation of distinctive antigens from apoptotic pathogenic T cells by macrophages and dendritic cells leading to the induction of an anticlonotypic response by cytotoxic T cells. Induction by photopheresis of apparently opposite immune processes (i.e. upregulation of an antitumor response and downregulation of allogeneic or autoimmune responses) can be explained by its ability to target either a single malignant T-cell clone (as in CTCL) or multiple activated T-cell clones (as in organ transplant rejection, graft-versus-host disease, or autoimmune disease). Because acute inflammation and T-cell activation may be important in the pathogenesis of restenosis following percutaneous transluminal coronary angioplasty (PTCA), photopheresis was used for the first time at our center to prevent restenosis. A total of 78 patients with single-vessel coronary artery disease amenable to PTCA with or without stent deployment were enrolled, 41 in the control group and 37 in the photopheresis group. Clinical restenosis occurred in significantly less photopheresis patients than control patients (8 vs 27%; p = 0.04), with a relative risk of 0.30 (95% confidence interval, 0.09-1.00). A multicenter clinical trial following a US FDA-recommended protocol is currently underway to better determine what, if any, impact photopheresis has in preventing restenosis.