Asymmetric Overgrowth and a Facial Port Wine Stain Seiringer, Peter; Biedermann, MD, Tilo; Schnopp, MD, Christina
The Journal of pediatrics,
February 2021, 2021-02-00, 20210201, Letnik:
229
Journal Article
Atopic dermatitis (AD) is a complex skin disease frequently associated with other diseases of the atopic diathesis. Recent evidence supports the concept that AD can also recognize other ...comorbidities, such as chronic inflammatory bowel or cardiovascular diseases. These comorbidities might result from chronic cutaneous inflammation or from a common, yet-to-be-defined immunologic background leading to immune deviations. The activation of immune cells and their migration to the skin play an essential role in the pathogenesis of AD. In patients with AD, an underlying immune deviation might result in higher susceptibility of the skin to environmental factors. There is a high unmet medical need to define immunologic endotypes of AD because it has significant implications on upcoming stratification of the phenotype of AD and the resulting targeted therapies in the development of precision medicine. This review article emphasizes studies on environmental factors affecting AD development and novel biological agents used in the treatment of AD. Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti–IL-4 receptor α-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players. These targeted molecules can be expressed on or drive the cellular players infiltrating the skin (eg, T lymphocytes, dendritic cells, or eosinophils). Such approaches can have immunomodulatory and thereby beneficial clinical effects on the overall skin condition, as well as on the underlying immune deviation that might play a role in comorbidities. An effect of these immunologic treatments on pruritus and the disturbed microbiome in patients with AD has other potential consequences for treatment.
Importantly, IgE reactivity with alpha-Gal could be completely blocked by pre-incubating the serum with pork-kidney extracts, proving IgE cross-reactivity (Fig 2). ...reactivity to pork meat using ...the ImmunoCAP assay was also completely blocked by pre-incubation with both pork-kidney extract and bovine thyroglobulin, demonstrating that in these patients, IgE recognition of the meat extract depends on IgE to alpha-Gal.
Background Component resolution recently identified distinct sensitization profiles in honey bee venom (HBV) allergy, some of which were dominated by specific IgE to Api m 3 and/or Api m 10, which ...have been reported to be underrepresented in therapeutic HBV preparations. Objective We performed a retrospective analysis of component-resolved sensitization profiles in HBV-allergic patients and association with treatment outcome. Methods HBV-allergic patients who had undergone controlled honey bee sting challenge after at least 6 months of HBV immunotherapy (n = 115) were included and classified as responder (n = 79) or treatment failure (n = 36) on the basis of absence or presence of systemic allergic reactions upon sting challenge. IgE reactivity to a panel of HBV allergens was analyzed in sera obtained before immunotherapy and before sting challenge. Results No differences were observed between responders and nonresponders regarding levels of IgE sensitization to Api m 1, Api m 2, Api m 3, and Api m 5. In contrast, Api m 10 specific IgE was moderately but significantly increased in nonresponders. Predominant Api m 10 sensitization (>50% of specific IgE to HBV) was the best discriminator (specificity, 95%; sensitivity, 25%) with an odds ratio of 8.444 (2.127-33.53; P = .0013) for treatment failure. Some but not all therapeutic HBV preparations displayed a lack of Api m 10, whereas Api m 1 and Api m 3 immunoreactivity was comparable to that of crude HBV. In line with this, significant Api m 10 sIgG4 induction was observed only in those patients who were treated with HBV in which Api m 10 was detectable. Conclusions Component-resolved sensitization profiles in HBV allergy suggest predominant IgE sensitization to Api m 10 as a risk factor for treatment failure in HBV immunotherapy.
Background A subgroup of patients with chronic spontaneous urticaria (CU) exhibits IgE antibodies directed against autoantigens, such as thyroperoxidase (TPO). We conducted this study to investigate ...whether such patients with CU with IgE against TPO benefit from treatment with omalizumab, a humanized anti-IgE mAb licensed for the treatment of severe persistent allergic (IgE-mediated) asthma. Objectives We sought to assess the efficacy of omalizumab treatment in patients with CU with IgE autoantibodies against TPO. Methods In this multicenter, randomized, double-blind, placebo-controlled study patients with CU (male/female, 18-70 years of age) with IgE autoantibodies against TPO who had persistent symptoms (wheals and pruritus) despite standard antihistamine therapy were randomized to receive either omalizumab (75-375 mg, dose determined by using the approved asthma dosing table) or placebo subcutaneously once every 2 or 4 weeks for 24 weeks. The primary end point was the change from baseline in mean weekly urticaria activity score after 24 weeks of treatment, as calculated from patients’ diaries. The safety and tolerability of omalizumab were also assessed. Results Of the 49 randomized patients (omalizumab, n = 27; placebo, n = 22), 42 completed the study. At week 24, patients demonstrated a mean reduction in the weekly urticaria activity score from baseline of 17.8 with omalizumab and 7.9 with placebo ( P = .0089). Complete protection from wheal development was observed in 19 (70.4%) patients in the omalizumab group compared with only 1 (4.5%) patient in the placebo group. The rate of adverse events was similar in both groups. Conclusions The results of this study indicate that omalizumab is an effective treatment option for patients with CU with IgE autoantibodies against TPO who are refractory to conventional treatment.
Background Atopic dermatitis (AD) is a T cell–mediated inflammatory skin disease, with TH 2 cells initiating acute flares. This inflamed skin is immediately colonized with Staphylococcus aureus , ...which provides potent Toll-like receptor (TLR) 2 ligands. However, the effect of TLR2 ligands on the development of TH 2-mediated AD inflammation remains unclear. Objective We investigated the progression of TH 2 cell–mediated dermatitis after TLR2 activation. Methods Using models for acute AD with TH 2 cells initiating cutaneous inflammation, we investigated the consequences of TLR2 activation. Dermatitis, as assessed by changes in ear skin thickness and histology, was analyzed in different BALB/c and C57BL/6 wild-type and knockout mouse strains, and immune profiling was carried out by using in vitro and ex vivo cytokine analyses. Results We show that TH 2 cell–mediated dermatitis is self–limiting and depends on IL-4. Activation of TLR2 converted the limited TH 2 dermatitis to chronic cutaneous inflammation. We demonstrate that the concerted activation of TLR2 and IL-4 receptor on dendritic cells is sufficient for this conversion. As an underlying mechanism, we found that the combinatorial sensing of the innate TLR2 ligands and the adaptive TH 2 cytokine IL-4 suppressed anti-inflammatory IL-10 and consequently led to the exacerbation and persistence of dermatitis. Conclusion Our data demonstrate that innate TLR2 signals convert transient TH 2 cell–mediated dermatitis into persistent inflammation, as seen in chronic human AD, through IL-4–mediated suppression of IL-10. For the first time, these data show how initial AD lesions convert to chronic inflammation and provide another rationale for targeting IL-4 in patients with AD, a therapeutic approach that is currently under development.
Abstract Purpose This study aimed to assess the safety, efficacy, and patient satisfaction of superficial radiation therapy in the treatment of Peyronie's disease (PD) in a retrospective analysis. ...Methods and materials We performed a retrospective analysis of 83 patients who underwent radiation therapy between 1999 and 2008 with 8 fractions of 4 Gy over a period of 6 months. With a mean follow-up time of 52 months, patients responded to a comprehensive questionnaire that covered patient characteristics, disease duration before radiation therapy, course of disease, treatment response, side effects, and patient satisfaction. Results After a mean follow-up time of 52 months, 78% of the treated patients reported that PD progression had stopped. Furthermore 47% of patients had a symptom regression. Only 7% of patients reported PD progression. The penile curvature was improved in 49% of patients, and plaque induration could be reduced in 42% of patients. Moreover, 71% of patients reported substantial pain relief, as measured by a visual analogue scale (1 = not satisfied; 10 = very satisfied). Treatment satisfaction was rated with a median of 8 in a visual analogue scale out of 10. Side effects included transient erythema in 38.6% of patients and 9.6% reported of transient or chronic dryness. No severe side effects were observed. Conclusions Radiation therapy for PD in the disease's early stages proved to be a safe and well-tolerated method with good results in pain relief, especially in patients aged <62 years. No serious adverse events or malign transformations are expected using doses up to 32 Gy.
For wasp venom immunotherapy, a protection rate of 92% was reported.4 In Europe, guidelines (eg, according to the European Academy of Allergy and Clinical Immunology and the German Society of Allergy ...and Clinical Immunology) propose that sting challenge tests should be carried out to identify those patients in whom standard venom immunotherapy (100 microg) is not effective.4 Based on the assumption that wasp stings are able to also boost sensitization to the venom and counteract the beneficial effects of immunotherapy, sting challenge tests are recommended only during ongoing venom immunotherapy. Patients included n = 57 Sex ratio (M/F) 1.2:1 (31/26) Age (y) (mean) Men 49.8 (range, 21-75) Women 51.9 (range, 28-78) No. of anaphylactic reactions in medical history (%) 1 event 64.9 2 events 24.1 3 or more events 10.5 Severity of anaphylaxis (according to Mueller) (%) Grade I 17.5 Grade II 17.5 Grade III 14 Grade IV 51 Time between last anaphylaxis and consultation with an allergologist (median) 55 d (range, 0 d to 25 y) Time between consultation and initiation of immunotherapy (median) 146 d (range, 12 d to 6.5 y) Immunotherapy experience (y) (median) 3.0 (range, 2.4-12.1) Inadvertent field sting 10.5% (n = 6) Sex ratio (M/F) 5:1 Experience of failure of immunotherapy (%) 8.8 (n = 5) Anphylaxis after field sting 3.5 (n = 2) Anphylaxis after sting challenge test 5.3 (n = 3) Atopic patients (%) 19.3 Elevated tryptase levels or mastocytosis (%) 14.0 Bee venom allergy (as a second allergy) (%) 5.3 Table I Patients' characteristics at baseline 4 weeks before the sting challenge testlow * F, Female; M, male.
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