Analysis of c-kit exon 11 and exon 17 of urticaria pigmentosa that occurred in monozygotic twin sisters

Genomic DNA extracted from peripheral blood mononuclear cells of monozygotic twin patients with urticaria pigmentosa was investigated for mutations of proto-oncogene c-kit. Neither the patients nor their families had genomic mutations in exon 11 or exon 17 of c-kit. The patients did not have any systemic involvement or bone marrow abnormalities. There are indications that some genetic factors may participate in the pathogenesis of urticaria pigmentosa in monozygotic twins. In the present patients, factors other than genomic faults in exon 11 and exon 17 of c-kit may be responsible for the pathogenesis.     

带状分布的色素性荨麻疹

报告1例带状分布的色素性荨麻疹.患者女,17岁.双侧腰腹部各见一条呈带状分布的色素沉着斑,用手摩擦后局部出现红色风团.皮损组织病理检查:表皮基底层黑素增加,甲苯胺蓝染色示真皮内毛囊及汗腺周围小片状肥大细胞浸润,胞质内含有嗜异染颗粒.     

成人色素性荨麻疹一例

患者,女,23岁。全身浅褐色斑片4年,皮肤划痕征(+),Darier征(-)。皮损组织病理示:真皮乳头层和真皮浅层血管周围可见灶状分布的圆形和梭形肥大细胞。甲苯胺蓝染色(+)。诊断:色素性荨麻疹。     

Familial urticaria pigmentosa associated with thrombocytosis as the initial symptom of systemic mastocytosis and Down''s syndrome

Most cases of urticaria pigmentosa are confined to the skin, but visceral involvement and/or haematological abnormalities have been observed. It is still a matter of debate whether all forms of mastocytosis are true neoplasias or reactive hyperplasias. Familial inheritance of urticaria pigmentosa is rare. We report on a fraternal set with urticaria pigmentosa as part of a systemic mastocytosis. The first patient additionally revealed persistent thrombocytosis and splenomegaly. His brother developed urticaria pigmentosa, intermittent diarrhoea, hepatomegaly and asthma bronchiale associated with trisomy 21 (Down's syndrome). The association of mastocytosis with thrombocytosis has seldom been described. In our patient it preceded the development of systemic mastocytosis. The association with Down's syndrome has not been reported until now.     

Cutaneous mastocytosis in children: a clinical analysis of 71 cases

OBJECTIVE: To characterize the clinical features, response to therapy, evolution and prognosis of cutaneous mastocytosis in children. BACKGROUND: Mastocytosis in children, instead of being induced by a potentially oncogenic c-kit mutation, is probably a clonal disease with benign prognosis. METHODS: The clinicopathological features, evolution and response to treatment were analysed in 71 children with mastocytosis. RESULTS: There were 53 (75%) cases of urticaria pigmentosa, 12 (17%) cases of mastocytoma, and six (8%) cases of diffuse cutaneous mastocytosis. In 92% of cases disease onset was in the first year of life. There was a male predominance 1.8 : 1. Treatment did not modify the disease evolution. Eighty per cent of patients improved or had spontaneous resolution of the disease. CONCLUSION: The most frequent clinical form of mastocytosis was urticaria pigmentosa followed by mastocytoma and diffuse cutaneous mastocytosis. Darier's sign was present in 94% of cases. A negative Darier's sign does not rule out mastocytosis. In contrast to adults, mastocytosis in children usually has a benign course making sophisticated or invasive diagnostic tests unnecessary. A classification of paediatric cutaneous mastocytosis is proposed.     

The cosmetic treatment of urticaria pigmentosa with Nd:YAG laser at 532 nanometers

Background Urticaria pigmentosa is a cutaneous disorder involving infiltration of the skin with mast cells. Histologically the papillary dermis has an increased number of mast cells with an increase in basal layer pigmentation. In addition to possible systemic symptoms, patients with urticaria pigmentosa can suffer emotionally from the cosmetic nature of this skin disease. Objective The purpose was to investigate the use of a diode‐pumped Nd:YAG laser at 532 nm for the treatment of the cosmetic comorbidity of urticaria pigmentosa lesions. Methods A 19‐year‐old white male with urticaria pigmentosa had multiple lesions on the dorsum of the hands and forearms. A test site on the right inner arm was treated with a DioLite? 532 nanometer laser. Because of satisfaction with the treatment of the test site lesions, multiple lesions on the dorsal hands and forearms were also treated with the DioLite? 532 nanometer laser. Results There was a dramatic clinical reduction in the amount of lesions on the dorsum of the hands and forearms. The test site lesions on the right inner arm had not recurred. Conclusion The diode‐pumped Nd:YAG laser at 532 nanometers should be considered part of a dermatologist's armamentarium for the treatment of a patient's cosmetic concerns with lesions of cutaneous mastocytosis.     

伴中性粒细胞浸润的色素性荨麻疹

报告1例伴中性粒细胞浸润的色素性荨麻疹．患儿女,5岁。躯干、四肢色素沉着斑伴瘙痒1年余．体格检查示躯干、四肢广泛分布大量色素性斑片及少量红斑、抓痕．组织病理检查示真皮内大量中性粒细胞浸润及核尘,未见血管纤维素样坏死．高倍镜下见血管周围较多肥大细胞浸润．诊断为伴中性粒细胞浸润的色素性荨麻疹。     

A clinical and histological study of urticaria pigmentosa: relationships between mast cell proliferation and the clinical and histological manifestations

In 21 cases of urticaria pigmentosa (UP), clinical and histological observations and evaluation of mast cell (MC) volume density in the lesions using a morphometric point counting method were performed. The mutual correlations between clinical and histological findings were statistically assessed by a method of multiple regression analysis. Clinical items employed in the analyses were as follows: sex, the age of onset, the age of biopsy, the biopsy, the duration of lesions, the type of skin lesions, sites involved, the presence or absence of Darier's sign of Darier's sign and symptoms, and serum histamine level. Histological items included the localization and infiltration pattern of MC, the level of basal melanosis, the presence or absence of inflammatory cell infiltration, and the MC volume density in the lesions. Statistical significance of the partial regression coefficients was obtained for 6 pairs of the criteria (p = 0.05), including the age of onset and the age of biopsy, the age of onset and the level of basal melanosis, the duration of lesions and the level of basal melanosis, and the type of skin lesions and the level of basal melanosis. No significant correlations were observed between the MC volume density in the lesions and any of the other items. These results suggest that the basal melanosis in a UP lesion may not be a direct reaction to the transitory massive infiltration of MC, but rather be due to a relatively long-term effect of MC infiltration. Furthermore, the MC volume density in the lesion is not likely to be an important factor in determining the clinical manifestations of a UP lesion.     

In vitro reactivity of mast cells in urticaria pigmentosa skin

The aim of our study was to evaluate the sensitivity of skin mast cells from urticaria pigmentosa (UP) patients to substance P (SP), tumor necrosis factor α (TNF-α) and anti-IgE, and to compare the sensitivity of these cells with that of skin mast cells from healthy human donors. Mast cells for in vitro functional studies were obtained using an enzymatic dispersion technique from skin biopsies (from 11 patients with UP and 11 healthy donors), and the reactivity of these cells was estimated on the basis of histamine release. Our observations indicated that UP skin mast cells and healthy skin mast cells had similar sensitivities to challenge with TNF-α at a concentration 10 ^–7 M (16.4% vs 15.2%) and with anti-IgE at a dilution 1:100 (41.0% vs 37.0%). However, UP mast cells showed considerably higher sensitivity to challenge with SP at a concentration 10 ^–4 M than healthy skin mast cells (20.0% vs 6.8%), and the difference was statistically significant ( P < 0.001). UP skin mast cells also demonstrated significantly higher spontaneous histamine release than healthy skin mast cells (32.1% vs 12.4%, P < 0.001). Our findings indicating UP skin mast cell sensitivity to SP might suggest that mechanisms involving neurogenic inflammation could contribute to the course of this disease. Received: 13 February 1997     

Mastocytosis: recent advances in defining the disease

Mastocytosis is a rare disease characterized by a primary pathological increase in mast cells in different tissues, which may present in a variety of clinical patterns. Major advances have been made in recent years in the understanding of the pathogenesis of mastocytosis. This review is aimed at familiarizing dermatologists with these recent findings, and at exploring their possible implications for the diagnosis and treatment of the condition. The heterogeneous clinical presentation of mastocytosis is detailed with respect to the type of skin lesions, age at onset, family history, organ systems involved, associated haematological disorders and prognosis. Recent genetic findings also indicate different pathogenetic forms of mastocytosis, as adult patients and those with associated haematological diseases usually express activating mutations of the stem cell factor receptor c-kit, whereas most cases of childhood-onset and familial mastocytosis seem to lack these mutations. Despite the presence of c-kit mutations, patients with cutaneous lesions generally have a good prognosis, even when there is involvement of other organs. Some patients, particularly those with childhood-onset disease, experience spontaneous remission, mostly by puberty. c-kit mutations do not explain the initial cause of mastocytosis, and their prognostic significance is as yet unclarified, as is the pathogenesis in patients without the mutations. Furthermore, these novel findings have as yet not resulted in a more effective treatment of the cause of the disease, so that counselling, prevention of exposure to mast cell secretory stimuli, and symptomatic treatment remain the mainstays of current patient management.     

斑驳病c-kit基因突变检测

目的：检测2例散发斑驳病患儿及其父母c-kit基因的突变情况。方法：收集2例斑驳病患儿及其父母的临床资料,提取其外周血DNA,采用PCR扩增c-kit基因编码区的全部外显子,DNA直接测序,明确突变位点。针对所发现的突变位点以TaqⅠ酶及SmaⅠ酶进行限制性内切酶检测。结果：2例患儿c-kit基因分别于第1862位C→A及第1784位T→C,使密码子GCT→GAT和CTG→CCG,导致Ala621Asp及Leu595Pro突变。2例患儿父母以及50名健康对照者不存在此两种基因突变。结论：Ala621Asp及Leu595Pro均为新生（denovo）突变,此突变是2例散发斑驳病患儿的主要病因。     

一家族性毛发上皮瘤家系CYLD1基因突变的研究

目的:收集山东一多发性家族性毛发上皮瘤家系,通过直接测序法检测该家系圆柱瘤病肿瘤抑制基因(cylindromatosis tumor-suppressor gene,CYLD1)第16、18号外显子是否存在突变。方法:提取家系成员外周血基因组DNA,利用PCR特异性扩增、直接测序方法对CYLD1基因的第16、18号外显子进行检测。结果:本家系成员的CYLD1基因第16、18号外显子未发现突变。结论:未发现本家族性毛发上皮瘤家系CYLD1基因第16、18号外显子存在突变,提示家族性毛发上皮瘤具有遗传异质性。     

c-kit蛋白在恶性黑素瘤中的表达

目的　探讨c kit蛋白在人恶性黑素瘤中的表达及临床意义 ,分析它和临床病理参数的关系。方法　采用免疫组化S P法检测 44例原发性皮肤恶性黑素瘤、9例转移性恶性黑素瘤及 2 0例良性痣中c kit蛋白的表达。结果　3 4例原发性皮肤恶性黑素瘤、4例转移性恶性黑素瘤、5例良性痣表达c kit蛋白 ,阳性率分别为 77.3 %、44 .4%、2 5 .0 % ,前者的阳性表达率显著高于后两者 (P均 <0 .0 5 ) ;原发性皮肤恶性黑素瘤中浅表扩散性恶性黑素瘤 (SSM )的c kit蛋白阳性表达率显著高于其它类型 (P均 <0 .0 1) ;c kit蛋白的表达与年龄 性别 发病部位 是否淋巴结转移等临床病理因素均无关 (P均 >0 .0 5 )。结论　c kit蛋白的表达可能与人恶性黑素瘤的发生发展有关 ,其有望成为治疗黑素瘤的有效靶向分子之一     

Antihistamines and alternatives in physical urticaria

ABSTRACT: The mainstay of management of physical urticaria is symptomatic therapy with H₁-type antihistamines, with preference being given to the nonsedating drugs. Patients vary in their responsiveness, in dependence of the type of physical urticaria. If even higher doses of H₁ blockers fail, dapsone, sulfazalazine, chloroquine, and danazol may be tried as alternatives. Corticosteroids, though highly effective, are contraindicated because of long-term adverse effects. Patients should also be advised to avoid eliciting stimuli or to use exposure only to induce the so-called hardening, under medical supervision. Physicians should exclude sustaining diseases or drug intake. In cold urticaria, a trial with antibiotics is worthwhile. If all these possibilities are utilized to the advantage of the individual patient, physical urticaria is a generally well-managed disease.     

水源性荨麻疹1例

报道1全13岁女孩，颜面、上肢、躯干上部在洗澡、洗脸等日常生活中接触水后数分钟内局部出风团，半小时后皮损消退，病程6年，无异位体质，发病与水温、日晒、运动无关。患者皮划痕症阴性。经曲尼斯特治疗略缓解。     

Phototherapy of urticaria pigmentosa: Clinical response and changes of cutaneous reactivity,histamine and chemotactic leukotrienes

Summary Ten patients with moderate to very severe urticaria pigmentosa were studied for the therapeutic effect of photochemotherapy (PUVA; six adults) and selective ultraviolet phototherapy (SUP; four adolescents). Despite a high mean PUVA dosage (138.6 ±63.4 J/cm²), only two patients had a very good response, while three had a good response and one had a fair response. On the reduction of the frequency of treatments, the symptoms gradually recurred, and several months after the discontinuation of therapy, the clinical status had reached the level prior to PUVA. The results with SUP were even less encouraging. A number of biophysical and biochemical parameters of the skin were studied in five patients before PUVA treatment, immediately after several months of PUVA treatment and again 5 months after the discontinuation of PUVA treatment. Weal and erythema reactions to intracutaneous skin tests remained unchanged after PUVA, while wealing with topically applied dimethylsulfoxide (DMSO) decreased. Transepidermal water loss was markedly reduced over DMSO weals. Histamine levels, which were elevated in lesional but not in normal skin, dropped with PUVA treatment, but after the discontinuation of treatment, they increased again in the lesions. On reverse-phase high-performance liquid chromatography, two main chemotactic factors, leukotriene B₄ and 5-HETE, were identified in lesional skin. Chemotactic activity was elevated in both lesional and uninvolved patient skin, reached normal levels at both sites after PUVA and maintained these low levels for several months after the discontinuation of treatment. Our data suggest that PUVA has reversible anti-inflammatory effects on human skin, because it increases epidermal-barrier function and decreases the synthesis of mediators of inflammation. These observations show the transitory therapeutic benefit of PUVA in patients with urticaria pigmentosa.     

Phenotypic characterization of skin lesions in urticaria pigmentosa and mastocytomas

In order to identify possible cellular abnormalities in human mastocytosis, sections from 13 urticaria pigmentosa lesions and 5 mastocytomas were compared with 5 normal skin specimens using histochemical, enzyme histochemical and immunohistochemical techniques. All toluidine blue-positive mast cells also reacted with FcRI and c-kit antibodies, almost all stained for tryptase, many for chymase and the myeloid workshop mast cell antibodies, few for FcRII and none for the proliferation marker Ki-67. Urticaria pigmentosa lesions contained fewer epidermal Langerhans cells and a lower percentage of avidin-positive mast cells than mastocytomas and normal skin. Mastocytomas exhibited generally weaker staining for mast cell markers and mostly lacked FcRI-bound IgE on mast cells and Langerhans cells, although the receptor was able to bind IgE in tissue sections. Most of the mast cell antibodies also reacted with other cell types. Only toluidine blue, avidin, tryptase and chymase stains were mast cell specific. Mast cells in mastocytosis thus differed only to a minor degree from normal mast cells, although distinct pathomechanisms may play a role in urticaria pigmentosa and mastocytosis.     

178例急性自发性荨麻疹转归为慢性的危险因素回顾性分析

目的：分析影响急性自发性荨麻疹（ASU）转归为慢性自发性荨麻疹（CSU）的危险因素。方法：回顾性分析本院2018年11月至2019年10月178例ASU患者的人口学信息、发病季节、初发病程、自诉可疑过敏原、自体血清皮肤试验（ASST）、7日荨麻疹活动度评分（UAS7）、血常规、血清总IgE测定、治疗药物,Logistic回归分析ASU转归为CSU的危险因素。结果：178例ASU中42例（23.60%）转归为CSU,单因素分析自诉食物过敏（P<0.001）、 ASST试验阳性（P<0.001）、初发病程（P＜0.001）与ASU患者转归为CSU具有相关性;多因素Logistics回归分析示自诉食物过敏（P=0.029）、ASST试验阳性（P=0.043）、初发病程长（P＜0.001）均是影响ASU转归为CSU的独立危险因素。结论：食物过敏、ASST试验阳性、初发病程长是ASU患者转归为CSU的危险因素。