沙利度胺治疗结节性痒疹

结节性痒疹是以瘙痒性结节为临床特征的慢性炎症性皮肤病,病因不明,目前尚无理想的治疗方法。本病由于症状明显、病程长,严重影响患者健康和生活质量;并使临床医师感到困惑。目前已有较多报道显示小剂量沙利度胺(≤100mg/d)对顽固性结节性痒疹的治疗具有较高的有效性和安全性。治疗过程中,需密切观察沙利度胺的不良反应,尤其是外周神经炎,一旦发生需立即停用。     

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.     

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。     

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。     

Dupilumab for prurigo nodularis: Case series and review of the literature

Dupilumab is a recombinant complete human monoclonal antibody modulating the signaling of interleukin‐4 and interleukin‐13 pathways and has been approved for the treatment of moderate/severe atopic dermatitis. Here, we present three cases of prurigo nodularis treated off‐label with dupilumab, and a review of the existing literature. All patients in this study had longstanding severe disease and had tried multiple treatment modalities. They were treated with dupilumab at an initial dose of 600 mg subcutaneously, followed by 300 mg every 2 weeks. Systematic literature searches were performed to identify literature describing the evaluation of the effect of treatment with dupilumab in prurigo nodularis. The physician's assessment of the patients revealed a good or excellent response to the treatment with dupilumab. Patients were evaluated after treatment for 4 and 7 months. Treatment was generally well‐tolerated; one in three patients reported dry eyes. Four studies with a total of 11 patients (range: 1–4) were identified by the literature search. Complete response was noted in all 11 patients. Treatment with dupilumab appears to be safe and well‐tolerated with clinical benefit in recalcitrant prurigo nodularis. Larger randomized and controlled trials using validated outcome measures are needed before dupilumab could be applied in clinical settings.     

Thalidomide treatment of prurigo nodularis

Four patients with classic recalcitrant prurigo nodularis had symptomatic and physical responses to thalidomide with remissions. Three of the four patients had increased IgE levels that decreased during therapy. In two patients, short-term treatment (2 to 3 months) was not sufficient to produce remission, but retreatment was effective. Two patients had long-term remission with more than 6 months of treatment. No significant side effects occurred.     

Treatment of prurigo nodularis with lenalidomide

Prurigo nodularis (PN) is an intensely pruriginous dermatological disorder whose treatment is challenging for dermatologists. It is characterized by eruptions of papules and hyperkeratotic nodules, some of which are eroded, on the extensor surfaces of the limbs. The most commonly used treatments for this condition are oral antihistamines and topical or systemic steroids. Thalidomide is an effective treatment option in cases of recalcitrant PN; however, its most frequent adverse effect is neurotoxicity, which often results in its discontinuation. Lenalidomide is an analogue of thalidomide that is more powerful and associated with less neurotoxicity than thalidomide. We report the third case of PN treated with lenalidomide, which involved a patient who was refractory to thalidomide. Lenalidomide may be a more effective treatment for PN than thalidomide and has a more favorable side effects profile than its counterpart.     

An observational analysis of low-dose thalidomide in recalcitrant prurigo nodularis

Thalidomide has been used as an effective treatment for prurigo nodularis (PN) with a median dose of 200 mg, but the risk of peripheral neuropathy precludes long-term use. We analysed the efficacy of low-dose thalidomide (< 100 mg) in 17 patients with recalcitrant PN. Patients were initiated on thalidomide 50 mg on alternate days, and the dose was increased (doubled) in a stepwise manner, if needed, until a ≥ 50% reduction in score (partial response; PR) on a visual analogue scale (VAS) was achieved. Thalidomide then was continued at the same dose for 4 weeks to achieve ≥ 90% decrease in VAS score; if this was not achieved, the dose was increased to a maximum of 100 mg and continued until complete resolution of lesions (complete response; CR). Four patients discontinued thalidomide due to adverse effects. Four patients achieved PR, while 9 patients (n = 2 with 50 mg, n = 7 with 100 mg) achieved CR. No patient developed neuropathy. In addition, complete responders achieved an earlier ≥ 50% reduction in VAS score. Two patients relapsed after 12 months but responded to thalidomide 50 mg.     

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.     

Peripheral neuropathy associated with nodular prurigo

Nodular prurigo is characterized by nodules and papules that are intensely pruritic. Thalidomide is used to treat patients with recalcitrant disease. Because thalidomide may cause peripheral neuropathy, it is current practice to perform nerve conduction studies to exclude subclinical neuropathy before treatment. The clinical record of eight patients with nodular prurigo, in whom thalidomide treatment was proposed, were looked at. Five of them showed evidence of subclinical neuropathy, thereby contraindicating the use of thalidomide. None of the patients had any symptoms of a peripheral neuropathy and none was taking any medications with a recognized potential to cause peripheral neuropathy. We propose that nodular prurigo may be associated with an underlying peripheral neuropathy in a subset of patients. In patients with nodular prurigo and demonstrable peripheral neuropathy, there may be a role for treatment with agents such as amitryptiline and gabapentin, which are normally used for neuropathic pain.     

Thalidomide-induced peripheral neuropathy. Effect of serum factor on nerve cultures

Sensory neuropathies developed in three of four patients with prurigo nodularis who had been treated with thalidomide. The serum samples of the patients who had neuropathy produced morphologic changes in cultured dorsal root ganglion cells. These observed changes support the postulate that thalidomide induces primary neuronal degeneration.     

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。     

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.     

Efficacy of UVA1 phototherapy in 230 patients with various skin diseases

OBJECTIVE: Investigation of the efficacy of ultraviolet (UV) A1 phototherapy on atopic eczema, scleroderma, granuloma annulare, urticaria pigmentosa, prurigo nodularis, lichen sclerosus et atrophicus, T-cell lymphoma, keratosis lichenoides chronica, chronic urticaria and some rare, sclerosing skin diseases. METHODS: The data of 230 patients treated with low-dose, medium-dose and high-dose UVA1 therapy during 6 years were retrospectively analysed. The mean single dose (J/cm(2)), the mean number of irradiations and the mean total dose (J/cm(2)) were evaluated. The efficacy of phototherapy was assessed by a grading scale and the number of patients was given in percentage for each group. RESULTS: Good therapeutic effects of UVA1 therapy were shown in patients with atopic eczema, scleroderma, lichen sclerosus et atrophicus, keratosis lichenoides chronica, prurigo nodularis and with cutaneous T-cell lymphoma. Positive effects in some patients were seen in the urticaria pigmentosa and granuloma annulare group, no change to slight improvement was seen in most of the patients with rare, sclerosing skin diseases and no effect was seen in the chronic urticaria group. CONCLUSION: Besides topical and systemic therapy, UVA1 radiation is a good option of treatment in various skin diseases. It is one of the first-line treatments for several sclerotic diseases and it often improves pruritus considerably.     

A case of severe actinic prurigo successfully treated with thalidomide

Actinic prurigo is an uncommon and usually persistent idiopathic photodermatosis with typical human leukocyte antigen (HLA) associations (HLA-DR4, particularly subtypes DRB1*0407 and DRB1*0401). Although its mechanism of action is not clearly understood, thalidomide has been shown to be particularly efficacious in treating actinic prurigo, among other conditions. A 31-year-old Australian woman who had suffered actinic prurigo for most of her life was treated with two courses of thalidomide (50-100 mg nocte) over consecutive summers. Remission was observed after cessation of the second course of thalidomide and had continued 4 years later. Abnormalities in the cutaneous response to ultraviolet radiation at the time of diagnosis, detected by monochromator phototesting, reverted to normal following treatment.     

Actinic prurigo (Hutchinson''s summer prurigo)

Actinic prurigo or Hutchinson's summer prurigo is an entirely separate disease from polymorphic light eruption. The former is especially common in Mexico, Central and South America, while the latter is common in Europe. The differences between the two conditions are enumerated. It is emphasized that actinic prurigo is a chronic persistent and recalcitrant eruption which often continues throughout the winter months and affects covered as well as exposed areas of skin. A personal series of 51 patients with actinic prurigo is presented. The efficacy of thalidomide in the treatment of some cases of actinic prurigo is confirmed.     

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.     

Thalidomide in 42 patients with prurigo nodularis Hyde

The aim of this study was to describe the use of thalidomide in the treatment of prurigo nodularis Hyde (PNH) refractory to other treatments or in cases where other treatments cannot be used due to side effects. 77 medical records were retrospectively reviewed for the following data: sex, age, age at the beginning of thalidomide treatment, dermatological diagnosis, duration of the skin disease, previous treatments, indications for treatment with thalidomide, effect of treatment, duration of treatment with thalidomide, reasons for cessation of thalidomide treatment, and side effects. 54 patients had PNH. All patients were refractory to standard therapy or had side effects to treatment. 42 patients were treated with thalidomide and the majority of patients experienced clinical improvement. The most common reason for discontinuation of therapy was side effects, the most frequent being peripheral neuropathy and sedation. Thalidomide effectively treats PNH refractory to standard medications. However, physicians must be aware of possible side effects, especially peripheral neuropathy.     

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.