Topical therapy and skin care for transplant-associated atopic dermatitis in children and adolescents.

BACKGROUND: New-onset allergic diseases, such as food allergy or atopic dermatitis, can develop after allogeneic transplantation. There are limited reports of new-onset atopic dermatitis after allogeneic hematopoietic stem cell transplantation in children and adolescents, and its treatment is yet to be established. The pathogenesis may differ from typical atopic dermatitis in terms of alloimmunity including graft-versus-host disease. METHODS: We present five children and adolescents with new-onset atopic dermatitis after allogeneic hematopoietic stem cell transplantation. The characteristics and clinical profiles of skin treatment after hematopoietic stem cell transplantation are summarized. RESULTS: Graft-versus-host disease prophylaxis included systemic tacrolimus for all patients. After hematopoietic stem cell transplantation, all patients achieved complete donor chimerism of the bone marrow and had acute graft-versus-host disease of the skin. After engraftment, all patients had skin lesions that met the international consensus diagnostic criteria for atopic dermatitis. None of the patients met the diagnostic criteria for chronic graft-versus-host disease. Topical therapy and skin care based on atopic dermatitis guidelines improved skin condition and atopic dermatitis severity scores in all patients. In addition, type 2 inflammatory markers improved accordingly. CONCLUSION: Topical therapy and skin care may be effective for transplant-related atopic dermatitis after hematopoietic stem cell transplantation. When extensive dermatitis is observed after hematopoietic stem cell transplantation, this treatment may avoid excessive immunosuppressive therapy if it meets the diagnostic criteria for atopic dermatitis.

Eosinophilic gastroenteritis with cytomegalovirus infection in an immunocompetent child.

A 3-year-old boy developed transient protein-losing gastroenteropathy associated with cytomegalovirus (CMV) infection. Both IgG and IgM antibodies to CMV were positive in a serologic blood test. Upper gastrointestinal endoscopy showed multiple erosions throughout the body of the stomach, without enlarged gastric folds. Histological examination of the biopsy specimens indicated eosinophilic gastroenteritis and CMV infection. The patient had complete resolution without specific therapy for CMV in four weeks. An allergic reaction as well as CMV infection played important roles in the pathogenesis of this case.

Acute IL-3 priming up-regulates the stimulus-induced Raf-1-Mek-Erk cascade independently of IL-3-induced activation of Erk.

IL-3 is a potent priming cytokine for human basophils, inducing an increase of mediator release after stimulation. The mechanism of IL-3 priming of the basophil response to FcepsilonRI aggregating stimuli remains unknown. We explored the regulation of several elements of IgE-mediated signaling by a short priming with IL-3. Early signaling events such as phosphorylation of Syk, Shc, linker for activation of T cells, and the calcium signal were not statistically affected by acute IL-3 priming. Downstream in the signaling cascade, a point of up-regulation was found at the level of Raf-1-Mek-Erk. Although the phosphorylation of Raf-1 was not changed by IL-3 priming, IL-3-primed anti-IgE-stimulated basophils showed a strong synergism for Mek and Erk phosphorylation when compared with either IL-3 or anti-IgE alone; pre-exposure to IL-3 induced a final 13-fold average increase over anti-IgE-induced Erk phosphorylation (6-fold above the sum of anti-IgE and IL-3 alone). The kinetics, dose response, and pharmacologic characteristics of the IL-3 priming of stimulus-induced Erk phosphorylation support the involvement of a yet unknown mechanism that is independent of IL-3-induced Erk and PI3K activation. This type of preactivation can be mimicked by incubation with the Ser-Thr kinase inhibitors, Ro-81-3220, or bisindoylmaleimide II.

Airway remodeling: a comparison between fatal and nonfatal asthma.

BACKGROUND: Airway remodeling has been recently one of the main goals in asthma research because it has been implicated to influence airway behavior and evolution of asthma; hence, important in long-term followup of asthmatic patients. METHODS: Airways of fatal asthma (n=3), non-fatal asthma (n=3) and control cases (n=4) were studied using morphometry and immunohistochemical and H&E staining. RESULTS: The basement membrane was thicker in the cartilaginous and membranous airways of fatal and non-fatal asthma groups compared to the control group (p<0.05). Smooth muscle shortening was greater in airways of fatal asthma cases while submucosal gland area and mucus plug occupying ratio were greater in fatal asthma large airways compared to the two other groups (p<0.01). Increased intact and degranulated mast cells were observed in smooth muscle and in submucosal gland of fatal asthma airways (p<0.01) and were associated with greater degree of smooth muscle shortening and larger submucosal gland area, respectively. Eosinophil and EG2+ cell infiltrations were greatest in lamina propria of airways of fatal asthma than in nonfatal and control cases (p<0.01), but were not associated with any airway structural change. CONCLUSION: Increased infiltration of eosinophils in the lamina propria and mast cells in smooth muscle and submucosal glands may have a role in airway remodeling of fatal asthma airways but needs further investigation. Moreover, mast cells in cartilaginous airways may participate in the regulation of smooth muscle tone and mucous gland secretion and hyperplasia.

Loss of syk kinase during IgE-mediated stimulation of human basophils.

BACKGROUND: Ongoing secretion from human basophils is a balance of activation and deactivation events. Recent studies have focused on downregulatory steps that appear to modify the presence of the activated state of various signaling molecules. We now examine downregulation regulated by mechanisms related to proteasome processing. OBJECTIVE: To determine the long-term effects of FcepsilonRI aggregation on expression of syk kinase. METHODS: Peripheral blood basophils were examined for changes in the expression of syk kinase after stimulation with optimal and suboptimal stimulation. RESULTS: Stimulation results in a 20% loss of syk in 1 hour and an 80% loss of syk in longer incubations (>18 hours). Loss of syk in this time frame can occur at levels of stimulation that do not result in observable mediator release. Loss of syk occurs after stimulation with either anti-IgE antibody or antigen. Activation is shown to result in c-Cbl phosphorylation, and its association with syk and immunoblotting reveals the appearance of a ladder of syk species with molecular weights that are consistent with ubiquitylation of syk. Stimulation in the presence of a proteasome inhibitor such as lactacystin A results in the sustained presence of very high-molecular-weight ubiquitylated species, although it does not alter the presence of the syk ladder. CONCLUSIONS: Although the loss of syk is probably too slow to account for downregulation of ongoing secretion of histamine or leukotriene C4 release, it may lead to longer-term alterations in basophil function that explain characteristics of clinical procedures like rapid drug desensitization.