Treatment of idiopathic prurigo nodularis in Taiwanese patients with low-dose thalidomide

Prurigo nodularis is an intensely pruritic dermatosis characterized by lichenified and excoriated papules and nodules. The course of prurigo nodularis is often chronic, and some patients respond very poorly to the standard therapeutic modalities. Because the pathogenesis of this disease remains obscure, the treatment of prurigo nodularis can be disappointing and frustrating for both the patients and physicians. Thalidomide, a tumor necrosis factor-alpha antagonist, has been suggested as an alternative treatment option for recalcitrant prurigo nodularis. In the past, the regimen for treatment of prurigo nodularis often required thalidomide at 200 mg/day. We recruited patients with intractable prurigo nodularis and treated them with low-dose thalidomide. Six patients with idiopathic prurigo nodularis were successfully treated with low-dose thalidomide (50-100 mg/day) without clinical development of peripheral neuropathy. In summary, our preliminary results suggest that low-dose thalidomide may be a safe and effective treatment option for patients with recalcitrant idiopathic prurigo nodularis.     

Dupilumab for pediatric prurigo nodularis: A case report

Herein we report on a 9‐year‐old girl with recalcitrant prurigo nodularis unresponsive to multiple standard treatments. She was started on dupilumab therapy with rapid improvement in pruritus within 2 weeks and near complete regression of lesions at 3 months. Dupilumab should be considered as an off‐label treatment for refractory prurigo nodularis in children.     

度普利尤单抗治疗成人结节性痒疹的疗效与安全性观察

【摘要】 目的 观察度普利尤单抗治疗结节性痒疹的疗效和安全性。方法 本研究为前瞻性研究。2021年1 - 10月在北京大学人民医院收集结节性痒疹患者,给予度普利尤单抗治疗。分别于第0、4、16周使用研究者整体评估（IGA）、数字评价量表（NRS）以及皮肤病生活质量指数（DLQI）评估疗效。用Wilcoxon符号秩检验和配对t检验对比分析治疗前后的评分变化。结果 共纳入17例患者,女12例,男5例,年龄（48.47 ± 16.26）岁。度普利尤单抗治疗16周时,NRS瘙痒评分由基线（8.00 ± 1.50）分降至（1.29 ± 0.85）分（t = 6.98,P＜0.001）,NRS睡眠影响评分由（5.18 ± 2.98）分下降至（0.12 ± 0.49）分（t = 12.55,P＜0.001）,DLQI指数由（13.29 ± 4.03）分降至（0.88 ± 0.70）分（t = 16.39,P＜0.001）;同时,所有患者由IGA 3 ~ 4级下降至IGA 0 ~ 2级,16例达到IGA 0 ~ 1级;12例达到IGA活动性0级。治疗过程中2例出现轻度结膜炎,1例出现局部注射反应,均在短暂对症处理后好转。结论 度普利尤单抗治疗成人结节性痒疹疗效显著且安全性良好。     

Combination therapy of fexofenadine and montelukast is effective in prurigo nodularis and pemphigoid nodularis

In this study, we report on the efficacy of combination therapy of second‐generation antihistamine antagonist, fexofenadine hydrochloride, and leukotriene receptor inhibitor, montelukast sodium, for the treatment of 15 prurigo nodularis or pemphigoid nodularis patients, in whom conventional therapy was ineffective. All patients received 10 mg montelukast once a day and 240 mg fexofenadine twice a day for 4 weeks in addition to other medications they had been taking. We assessed the manifestations of the lesions and itching intensity before and after the therapy, and we evaluated each patient as (i) markedly improved, (ii) improved, (iii) slightly improved, (iv) no change, (v) worse. Two patients (13.3%) were evaluated as markedly improved, and the lesions of one patient completely disappeared. Three patients (20.0%) were evaluated as improved, and six patients (40.0%) as slightly improved. Thus, 11 of 15 cases (73.3%) improved by combination therapy of fexofenadine and montelukast, in which nine cases (75.0%) of prurigo nodularis and two cases (66.7%) of pemphigoid nodularis were involved. No patients revealed any side effects. This study revealed that combination therapy of fexofenadine and montelukast was effective for some patients with conventional therapy‐resistant prurigo nodularis and pemphigoid nodularis.     

Terapia UVB de banda estrecha en prurigo nodular

—Introduction. Narrow-band UVB therapy, considered a first-choice treatment in psoriasis, has also been proposed as an effective alternative in other inflammatory dermatoses. The clinical experience obtained in a group of patients affected with prurigo nodularis treated with narrow-band UVB therapy is presented.Material and methodAn assessment was made of the clinical and symptomatic response, with no control group, of a series of 15 patients affected with prurigo nodularis who received a total of 22 cycles of narrow-band UVB therapy administered in a full-body cabinet.ResultsAfter an average number of 32 sessions and an average cumulative dose of 26.2 J/cm2, there was evidence of clinical and symptomatic improvement greater than 50 % in 73% of the therapeutic cycles completed (16/22), with 23% (5/22) considered to be in full remission.Discussion and conclusionsThe data provided suggests that narrow-band UVB therapy may be a well tolerated, moderately effective therapeutic alternative in prurigo nodularis.     

Topical vitamin D3 (tacalcitol) for steroid-resistant prurigo

Summary A topical vitamin D₃, ointment (tacalcitol) was prescribed for patients with long-histing pruriginous lesions (four with prurigo nodularis und seven with subacuLe prurigo, four of whom had atopic dermatitis). Seven of 11 cases had not responded to a topical steroid ointment and even to occlusive application of the ointment. Nine of 11 cases showed a significant clinical response to this new regimen within 4 weeks. Epidermal FceR1(+) dendritic cells were increased in number in prurigo nodularis and reduced to normal level after the therapy. Topical vitamin D₃ ointment might be an alternative therapy ibr steroid-resistant prurigo.     

沙利度胺对结节性痒疹患者血清TNF-α、IL-12的影响

目的:观察沙利度胺治疗结节性痒疹患者前后血清中肿瘤坏死因子-α(TNF-α)及白介素-12(IL-12)的变化。方法:50例结节性痒疹患者给予口服沙利度胺片治疗,测定治疗前后患者血清中TNF-α及IL-12水平,并与正常对照组比较。结果:治疗总有效率为78%。治疗前TNF-α及IL-12水平分别为(4.16±1.68)μg/m L及(65.74±19.58)pg/m L,均较正常对照者增高,差异有统计学意义(t值分别为3.78、4.05,P值均<0.05);治疗后分别下降至(2.78±1.24)μg/m L及(51.43±13.47)pg/m L,与治疗前比较差异均具有统计学意义(t值分别为2.52、2.38,P值均<0.05)。结论:沙利度胺可能通过降低血清TNF-α及IL-12水平起到治疗作用。     

Thalidomide treatment for prurigo nodularis in human immunodeficiency virus-infected subjects: efficacy and risk of neuropathy

OBJECTIVE: To evaluate safety and efficacy of thalidomide in the treatment of prurigo nodularis in a group of human immunodeficiency virus (HIV)-infected patients whose condition was recalcitrant to standard treatment. DESIGN: Prospective study. SETTING: Outpatient dermatology and neurology clinic, both referral settings.PATIENTS: Eight HIV-infected patients with refractory prurigo nodularis; a total of 10 met inclusion criteria, but 2 could not be followed up. INTERVENTIONS: Treatment with thalidomide, 100 mg/d. Subjects were randomized after 1 month to receive 100 or 200 mg/d. If side effects were noted, the drug was reduced to a tolerable dose or discontinued. Subjects were monitored at baseline and monthly for degree of pruritus and total area of body involvement of prurigo nodularis. Sequential neurologic assessments were performed. MAIN OUTCOME MEASURES: Efficacy and toxic effects. RESULTS: The dosage of thalidomide ranged from 33 to 200 mg/d. Eight subjects had a greater than 50% response in reduction of itch over 3.4 months (average). Seven subjects had a greater than 50% reduction of skin involvement over 5 months (average). Three subjects developed thalidomide peripheral neuropathy (TPN). There was no correlation between duration of treatment, daily or cumulative dose, and TPN. A change in the Neuropathy Impairment Score of 10 points was a good marker of TPN, as was a greater than 50% decrease in the sural sensory nerve action potential amplitude. CONCLUSIONS: Thalidomide reduced the signs and symptoms of prurigo nodularis in HIV-infected subjects. One third of subjects developed TPN, underscoring the importance of careful neurologic assessment.     

Dupilumab treatment improves quality of life in adult patients with moderate‐to‐severe atopic dermatitis: results from a randomized,placebo‐controlled clinical trial

Atopic dermatitis is a skin disease, commonly known as eczema. It affects up to 1 in 10 adults. Atopic dermatitis is usually very itchy, causing people to wake up at night, and feel “low”. This state of general discomfort is known as reduced quality of life. Dupilumab is a new treatment approved in the U.S.A. for adults with moderate‐to‐severe atopic dermatitis. The treatment blocks some of the mechanisms involved in the disease. In a clinical trial conducted in Europe, researchers observed 109 patients with moderate‐to‐severe atopic dermatitis. The patients received dupilumab over 12 weeks. They found that the treatment improved the eczema and its symptoms, such as itch. The researchers also studied how the treatment affected quality of life in 64 out of 109 patients in the study. These patients had answered a set of questions that measures how atopic dermatitis affects their quality of life (Quality of Life Index for atopic dermatitis [QoLIAD]). Thirty‐two patients received dupilumab 300 mg weekly, by injection under the skin, and 32 received placebo. About 6 out of 10 patients treated with dupilumab had better quality of life over the 12 weeks, whereas only about 1 in 10 placebo‐treated patients improved. The researchers also found a relatively strong link between improvements with dupilumab in QoLIAD score and improvements in the eczema and symptoms. Dupilumab was well‐tolerated by the patients. The authors conclude that dupilumab, a new breakthrough treatment for atopic dermatitis, improves eczema and its symptoms, and in turn, the patients’ quality of life.     

Omalizumab for atopic dermatitis: case series and a systematic review of the literature

Omalizumab is a recombinant humanized monoclonal antibody targeting the high‐affinity Fc receptor of IgE, registered for the treatment of chronic spontaneous urticaria and severe allergic asthma. We present a case series of nine patients with atopic dermatitis (AD) treated off‐label with omalizumab and a systematic review of the existing literature. Patients were selected consecutively from a tertiary dermatological referral center during a 5‐year period. All patients were treated with omalizumab at a starting dose of 300 mg subcutaneously every 4 weeks. Systematic literature searches were performed in PubMed, Web of Science, EMBASE, and ClinicalTrials.gov to identify any study (case reports, case series, and controlled trials) evaluating the effect of treatment with omalizumab in AD. Based on physicians’ assessment, 50% of our patients had a good or excellent response to treatment with omalizumab; a further 12.5% had a moderate response, while 37.5% experienced no response or deterioration of symptoms during treatment. Treatment was generally well tolerated. Twenty‐six studies with a median of four patients each (range 1–21), comprising 174 patients, were included in the systematic review. Summed over all studies, a total of 129 patients (74.1%) experienced a beneficial effect of treatment ranging from little to complete response. Omalizumab appears to be a safe and well tolerated, however expensive, treatment with some clinical benefit in patients with severe recalcitrant AD. Recommendation for use in clinical practice awaits evidence from larger randomized controlled trials.     

Dermoscopy of prurigo nodularis

The diagnosis of prurigo nodularis is mainly clinical, based on its distinctive features. However, in some cases it may be difficult to differentiate it from other nodular dermatoses only on the clinical basis, thus requiring histopathological examination to reach a definitive diagnosis. The aim of this study was to describe for the first time the dermoscopic features of prurigo nodularis and the useful contribution of dermoscopy in the differential diagnosis of such dermatoses. Fourteen patients with histopathologically proven prurigo nodularis were included in the study. The results of our study suggest that the detection of a “white starburst pattern” surrounding brown‐reddish/brown‐yellowish crust(s), erosion(s) and/or hyperkeratosis/scales is a useful clue to support the clinical diagnosis of prurigo nodularis, distinguishing it from the other main differential diagnoses.     

以结节性痒疹为首发表现的艾滋病3例及文献复习

结节性痒疹是艾滋病患者较为常见的皮肤表现,是多因素导致的疾病,其皮损与非艾滋病患者相似。本文3例均为男性,临床表现为全身散在丘疹、结节、表皮剥脱、结痂伴剧烈瘙痒,淋巴细胞分类计数示CD4、CD4/CD8比值降低。HIV血清抗体初筛实验及确证实验均(+)。皮损组织病理符合结节性痒疹。2例予抗组胺药物和外用糖皮质激素软膏后症状减轻,1例放弃治疗。沙利度胺是治疗艾滋病相关性结节性痒疹最有效的药物。     

Antipruritic effect of cyclosporine microemulsion in prurigo nodularis: Results of a case series

Background: Prurigo nodularis shows intense itching nodules, which are often persistent and therapy refractory. Histological alterations include fibrosis of collagen fibers and presence of inflammatory infiltrate, which partly explains the clinical persistence of lesions. Inflammatory cells may directly contribute to induction and maintenance of pruritus at nerve fibers. Cyclosporine microemulsion (ME) suppresses the migration and proliferation of inflammatory cells and may thereby interfere with pathogenesis of prurigo nodularis. The aim of this investigation was to assess the antipruritic efficiency of cyclosporine ME in therapy of prurigo nodularis. Patients and methods: 14 patients with prurigo nodularis of diverse origin and failure to previous therapy were treated with oral cyclosporine ME (3 to 5 mg per kg daily). Blood pressure, liver enzymes, renal function and differential blood count were monitored. Results: In 13 of 14 prurigo patients (92.9 %) there was a significant response to monotherapy with cyclosporine ME. The maximal antipruritic effect occurred after 2 weeks to 12 months. Prurigo nodules also healed during therapy. Seven patients (50.0 %) described side effects. In one case the therapy was stopped. Conclusions: Oral cyclosporine ME is an effective therapy for prurigo nodularis of diverse origin. It appears to function by inhibiting dermal inflammatory cells.     

Thalidomide experience of a major Australian teaching hospital

St Vincent's Hospital Melbourne cautiously prescribes thalidomide as a treatment for recalcitrant dermatoses. The guidelines used for prescribing and monitoring thalidomide for dermatological conditions at this institution are presented. Fourteen patients were treated with thalidomide (11 women, three men) over a 5‐year period. The diagnoses of patients treated were actinic prurigo, prurigo nodularis, lupus erythematosus and Behçet's syndrome. A clinical improvement was noted in 10 patients (71.4%) prescribed thalidomide. Cessation of thalidomide treatment occurred in seven patients (50%) because of adverse effects. Of the patients with adverse effects, four developed abnormal nerve conduction studies and three developed intolerable adverse events (such as dizziness and vomiting). Adverse effects from thalidomide treatment are common but, through vigilant treatment planning, patient education and regular monitoring, the risk of permanent peripheral neuropathy and teratogenicity from thalidomide toxicity can be minimized.     

沙利度胺联合复方氟米松软膏治疗结节性痒疹疗效观察

目的观察沙利度胺联合复方氟米松软膏治疗结节性痒疹疗效。方法将87例结节性痒疹患者随机分为两组。治疗组45例,口服沙利度胺50mg,2次/d,症状改善后逐步减量50mg或25mg,1次/d维持,联合外用复方氟米松软膏,1次/d,共8周;对照组42例,口服左西替利嗪片5mg,1次/d,联合外用复方氟米松软膏1次/d,共8周。结果治疗组有效率为91.11%,对照组为69.05%,两组有效率差异有统计学意义（P〈0.05）,均无明显不良反应。结论沙利度胺联合复方氟米松软膏治疗结节性痒疹安全可靠。     

Prurigo nodularis: a review

Prurigo nodularis is a chronic condition characterized by a papulonodular pruriginous eruption of unknown aetiology. This condition is a difficult disease to treat and causes frustration to both the patient and the treating doctor. A variety of systemic conditions have been reported to be associated with prurigo nodularis. The mechanism by which these disorders may trigger prurigo nodularis is unknown. Nerve growth factor has been implicated in the pathogenesis of prurigo nodularis. Calcitonin gene-related peptide and substance P immunoreactive nerves are markedly increased in prurigo nodularis when compared with normal skin. These neuropeptides may mediate the cutaneous neurogenic inflammation and pruritus in prurigo nodularis. Topical or intralesional glucocorticoids are the treatment of choice. Other topical treatments such as topical vitamin D3, and topical capsaicin have also been reported to be effective. Oral treatments such as cyclosporin and thalidomide have been shown to improve both appearance of the skin and pruritus. We review the clinical features, associations, pathology, pathogenesis and treatment of prurigo nodularis.     

Management of dupilumab‐associated conjunctivitis in atopic dermatitis

Since September 2017, the monoclonal antibody dupilumab (Dupixent^®) has been approved in the EU for the treatment of moderate‐to‐severe atopic dermatitis. By blocking IL‐4 and IL‐13 signaling pathways, dupilumab improves both objective signs and subjective symptoms of the disease. Blocking of the IL‐4aRα subunit leads to improvement of the skin's barrier function and reduction in Th2‐mediated inflammation. While the rate of adverse events on dupilumab is generally low, mild‐to‐moderate conjunctivitis associated with redness as well as a burning and foreign body sensation has been reported in up to 28 % of patients. Treatment options include topical corticosteroids and topical calcineurin inhibitors. The present review highlights the clinical presentation of dupilumab‐associated conjunctivitis and addresses pharmacological and non‐pharmacological options available for the treatment of this clinically highly relevant condition.     

Demonstration by S-100 protein staining of increased numbers of nerves in the papillary dermis of patients with prurigo nodularis.

BACKGROUND: We hypothesized that hyperplasia of papillary dermal nerves was a constant feature of prurigo nodularis. OBJECTIVE: We tested this hypothesis by examining sections from 25 cases of prurigo nodularis, 25 cases of skin lesions characterized by epidermal hyperplasia without clinical pruritus, and 22 cases of clinically pruritic dermatoses with variable degrees of epidermal response for the presence of papillary dermal nerves. METHODS: We used a standard immunohistochemical assay with an antibody to S-100 protein as a means of identification of nerves. RESULTS: In 24 of 25 cases of prurigo nodularis, papillary dermal nerves were identified by immunostaining. Cutaneous nerves were present in 1 of 22 cases of epidermal hyperplasia with pruritus and were absent in the papillary dermis in nonpruritic cases. CONCLUSION: We conclude that hypertrophy of cutaneous papillary dermal nerves is a relatively constant feature of prurigo nodularis. The presence of papillary dermal nerves suggests a neurocutaneous component in the pathogenesis of prurigo nodularis.     

度普利尤单抗治疗123例特应性皮炎的疗效及安全性分析

【摘要】 目的 探讨度普利尤单抗治疗特应性皮炎（AD）的临床疗效及安全性。方法 通过双向性研究分析2020年7月至2022年3月于中南大学湘雅二医院皮肤科接受度普利尤单抗治疗的123例AD患者的临床资料,评估度普利尤单抗的疗效及安全性。主要指标为治疗前、治疗4、8、12、16周的患者湿疹面积和严重程度指数（EASI）、瘙痒峰值数字评定量表（NRS）、以患者为导向的湿疹测量评分（POEM）和皮肤病生活质量指数（DLQI）评分,同时记录不良反应及不良事件。治疗前后各评分的比较采用配对样本t检验或重复测量资料的方差分析;不同类型皮损及不同IgE水平患者疗效比较采用Mann-Whitney U检验;采用基于稳健标准误的多元回归模型分析疗效的影响因素。结果 123例AD患者中,107例纳入疗效分析,85例（79.44%）完成了至少4周治疗,其中6例（7.06%）达EASI75,23例（27.06%）达EASI50,EASI、NRS、POEM、DLQI评分（10.41 ± 6.72、4.12 ± 1.74、8.60 ± 4.29、7.81 ± 4.38）均显著低于治疗前（18.08 ± 10.69、7.21 ± 2.01、16.88 ± 5.74、12.95 ± 5.95）,均P < 0.001。共47例（43.93%）完成了至少16周治疗,28例成人患者中23例（82.14%）、19例青少年及儿童中17例（89.47%）达EASI75及以上;治疗4、8、12、16周EASI、NRS、POEM、DLQI评分与治疗前相比差异均有统计学意义（均P < 0.001）,且第4、8、12、16周各评分均显著低于前一相邻时间点（均P < 0.05）。治疗4周时,伴结节性痒疹的AD患者EASI评分改善率显著低于不伴者（U = 151.00,P = 0.006）,而伴与不伴干皮症的AD患者间EASI评分改善率差异无统计学意义（P > 0.05）;治疗16周时,不同类型皮损患者间EASI评分改善率差异无统计学意义（均P > 0.05）。基于稳健标准误的多元回归分析显示,第16周时EASI改善程度与皮疹类型无关（β = 3.20,P = 0.075）,和年龄（β = -0.22,P = 0.030）、成年与否（β = 9.54,P = 0.049）、直系亲属家族史（β = 7.46,P = 0.017）具有相关性;NRS评分改善程度与皮疹类型（β = 0.55,P = 0.032）、年龄（β = -0.04,P = 0.033）、体重（β = -0.05,P = 0.020）、成年与否（β = 2.06,P = 0.003）、是否合并使用抗组胺药物（β = -1.91,P = 0.001） 具有相关性。不良反应：123例患者中,6例（4.88%）发生结膜炎,2例（1.63%）出现面部红斑。不良事件：1例右前额出现白癜风样改变,3例分别因过敏性紫癜、双上肢周围神经远端轴索损害、癫痫停药,与度普利尤单抗的相关性不确定。结论 度普利尤单抗治疗AD疗效显著,总体安全性好,可作为传统治疗欠满意患者的治疗新选择。     

中西医结合治疗结节性痒疹临床观察

目的探讨中西医结合治疗结节性痒疹的临床疗效。方法结节性痒疹湿热证患者94例,分为西医对照组45例和治疗组49例,两组患者均以西药常规治疗,对照组外用复方地塞米松霜,治疗组加用中药止痒汤并外用中成药冰黄肤乐软膏封包治疗,均10天为1个疗程,共用4个疗程。分别于第2、4个疗程结束后观察疗效,随访半年观察复发情况。结果两组有效率比较差异无显著性意义(χ2=1.92,P>0.05),但其治愈率、近期疗效、远期复发率和副作用方面,治疗组明显优于对照组。结论在西药治疗基础上加用中药止痒汤及冰黄肤乐软膏封包治疗对结节性痒疹具有良好的疗效。