Evidence linking atopy and staphylococcal superantigens to the pathogenesis of lymphomatoid papulosis, a recurrent CD30+ cutaneous lymphoproliferative disorder.
将特应性和葡萄球菌超抗原与淋巴瘤样丘疹病 (一种复发性CD30 + 皮肤淋巴组织增生性疾病) 发病机制联系起来的证据。
- 作者列表："Kadin ME","Hamilton RG","Vonderheid EC
BACKGROUND:Primary cutaneous CD30+ lymphoproliferative disorders (CD30CLPD) are the second most common type of cutaneous T cell lymphoma (CTCL) and include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Case reports and small patient series suggest an association of CD30CLPD with atopic disorders. However, the prevalence of atopy in patients with CD30CLPD in retrospective studies depends on patients' recall which is not always reliable. More objective criteria of atopy include evidence of skin reactivity to allergens (positive prick test) and evidence of allergen-specific IgE in serum. This study was undertaken to test the hypothesis that atopy is prevalent in patients with CD30CLPD using serologic criteria of allergen-specific IgE antibodies to aeroallergens and Staphylococcal aureus enterotoxin superantigens (SSAgs). METHODS:We tested serum samples of CD30CLPD for common IgE-specific airborne allergens with the Phadiatop test, which if positive, is regarded as serologic evidence of atopy in adults. Sera were also tested for IgE antibodies reactive to three Staphylococcal enterotoxins with superantigenic properties (SSAg-IgE). Control sera were obtained from adult subjects evaluated for rhino-sinusitis and a negative Phadiatop test. Patients' history of an atopic disorder was obtained by retrospective chart review. FINDINGS:Nearly 50% of patients with the most common LyP types (A and C) had a positive Phadiatop test for allergic sensitization to common airborne allergens, and total serum IgE (IgE-t) was increased compared to non-atopic controls. At the IgE antibody concentration generally used to define serologic atopy (≥ 0.35 kUA/L), 8/31 (26%) samples of CD30CLPD and 7/28 (25%) samples of LyP were reactive to at least one SSAg-IgE compared to 3/52 (6%) control specimens (P = 0.016 and P = 0.028, respectively). TSST1-IgE was detected in 7 (23%) specimens of CD30CLPD, often together with SEB-IgE; SEA-IgE ≥ 0.35 kUA/L was not detected. For control specimens, TSST1-IgE exceeded the 0.35 kUA/L threshold in 3 (6%) specimens. CONCLUSIONS:Patients with LyP types A and C have serologic evidence of atopy against common airborne antigens and SSAgs when compared to control adult subjects who had rhino-sinusitis and a negative Phadiatop test for aero-IgEs. Serologic evidence of atopy exceeded that determined by LyP patients' personal history. The findings support our hypothesis that an atopic diathesis may contribute to the pathogenesis of the most common types of LyP (A and C).
背景: 原发性皮肤CD30 + 淋巴增生性疾病 (CD30CLPD) 是皮肤T细胞淋巴瘤 (CTCL) 的第二常见类型，包括淋巴瘤样丘疹病 (LyP) 和原发性皮肤间变性大细胞淋巴瘤 (pcALCL)。病例报告和小患者系列提示CD30CLPD与特应性疾病的相关性。然而，回顾性研究中CD30CLPD患者中特应性的患病率取决于患者的回忆，这并不总是可靠的。特应性更客观的标准包括皮肤对过敏原反应性的证据 (点刺试验阳性) 和血清中过敏原特异性IgE的证据。本研究采用过敏原特异性IgE抗体和金黄色葡萄球菌肠毒素超抗原 (SSAgs) 的血清学标准，验证CD30CLPD患者普遍存在特应性的假设。 方法: 我们用Phadiatop试验检测了CD30CLPD血清样本中常见IgE特异性空气过敏原，如果阳性，则视为成人特应性的血清学证据。还检测了血清对三种具有超抗原性质的葡萄球菌肠毒素 (SSAg-IgE) 反应性的IgE抗体。对照血清来自评价鼻-鼻窦炎和Phadiatop试验阴性的成人受试者。通过回顾性图表回顾获得患者的特应性疾病史。 结果: 近 50% 的最常见LyP类型 (A和C) 患者对常见空气过敏原和血清总IgE (IgE-t) 的过敏致敏Phadiatop试验阳性与非特应性对照相比，was增加。在IgE抗体浓度下，通常用于定义血清学特应性 (≥ 0.35 kUA/L)，8/31 (26%) 个CD30CLPD样本和 7/28 (25%) 与 3/52 (6%) 例对照标本相比，LyP样本对至少一种SSAg-IgE具有反应性 (分别为P = 0.016 和P = 0.028)。7 例 (23%) CD30CLPD标本检出TSST1-IgE，常与SEB-IgE一起检出; SEA-IgE ≥ 0.35 kUA/L未检出。对于对照标本，在 3 个 (0.35) 标本中，TSST1-IgE超过 6% kUA/L阈值。 结论: lyP型A和C患者与鼻-鼻窦炎和pairiges Phadiatop试验阴性的对照成人受试者相比，具有针对常见空气抗原和ssag的特应性血清学证据。特应性的血清学证据超过了LyP患者个人病史确定的证据。这些发现支持了我们的假设，即特应性素质可能有助于最常见类型LyP (A和C) 的发病机制。
METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.
METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.
METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.