Clinical Characteristics and Gene Mutations in 186 Cases of Kindler Syndrome / 中国医学科学院学报

Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS. Methods The clinical data of one case of KS from Peking Union Medical College Hospital and 185 cases reported in literature were collected. The gene mutation types,patient clinical data,and tumor characteristics were statistically analyzed. Results A total of 186 cases were enrolled,including 110 males and 76 females,with the mean age of(28±16)years. The data of gene mutation and specific clinical manifestations were available in 151 and 94 patients,respectively. The main clinical manifestations of KS included poikiloderma,occurrence of blister in childhood,and photosensitivity,and the secondary clinical manifestations included oral inflammation,palmoplantar keratoderma,webbing/pseudoainhum,dysphagia,urethral stricture and so on.Oral inflammation(r=0.234,P=0.023),palmoplantar keratoderma(r=0.325,P=0.001),webbing/pseudoainhum(r=0.247,P=0.016),dysphagia(r=0.333,P=0.001),urethral stricture(r=0.280,P=0.006)were significantly correlated with age,showing significantly higher incidence in the patients over 32 years old.Urethral stricture(χ2=11.292,P=0.001)and anal stenosis(χ2=4.014,P=0.045)were significantly correlated with sex,with higher incidence in males.Eighty different mutations were found in 151 patients,and the most common gene mutation was c.676C>T.Forty-one tumors occurred in 27 patients,among which squamous cell carcinoma accounted for 92.7%. The gene mutation site had no significant correlation with squamous cell carcinoma or patient country. Conclusions The c.676C>T in FERMT1 gene is the most common mutation in KS.The patients are prone to squamous cell carcinoma and mainly attacked at the exposure sites(hand and mouth).

Clinical Analysis of Eight Cases of Pemphigus with High Titers of Anti-desmoglein Antibodies in Remission / 中国医学科学院学报

Objective To investigate the clinical manifestations,diagnosis,treatment,and laboratory examination characteristics of 8 pemphigus patients with high titers of anti-desmoglein antibodies in remission. Methods A retrospective study was conducted for the pemphigus patients diagnosed and treated in the department of dermatology from January 2013 to September 2020.The patients should have the serum anti-desmoglein antibodies ≥150 U/ml in remission or the antibody levels dropped less than 20%(calculated based on the maximum detection limit of 150 U/ml)of their initial ones detected before treatment,and the clinical and laboratory data of patients eligible for the inclusion criteria were collected. Results Among the 134 pemphigus patients with available follow-up data during this period,a total of 8 patients met the criteria,with the follow-up period of 21-85 months and the remission duration of 18-70 months.They all received less than or equal to 10 mg/d prednisone and had high titers of anti-desmoglein antibodies.At their first visit,the number of patients with positive anti-desmoglein 1/desmoglein 3 antibodies was 7.Two patients still had high titers of anti-desmoglein 1 antibodies 19 months and 21 months after they achieved remission,and 5 patients had high titers of anti-desmoglein 3 antibodies in 18-70 months.There was one patient showing high titers of both antibodies,especially for anti-desmoglein 1 antibodies.This patient relapsed after 19 months' remission while other patients were still in clinical remission. Conclusions Some pemphigus patients showed persistent high titers of anti-desmoglein antibodies in remission.Anti-desmoglein 3 antibodies were more common to keep positive,while high titer of anti-desmoglein 1 antibodies was less observed.The high titer of anti-desmoglein 1 antibodies had a correlation with recurrence.For the pemphigus patients with long-term clinical remission but high antibody titer,the dosages of corticosteroids should be adjusted carefully according to their actual clinical manifestations and the positive antibody type.For the patients with high titer of anti-desmoglein 1 antibodies,the dosage reduction of corticosteroids should be appropriately slower.

Clinical and Laboratory Features of 6 Cases of Pemphigoid Nodularis / 中国医学科学院学报

To investigate the clinical manifestations and laboratory characteristics of 6 cases of pemphigoid nodularis (PN). The clinical and laboratory data of 6 patients with PN admitted to the Department of Dermatology,Peking Union Medical College Hospital from January 2016 to August 2019 were retrospectively analyzed. PN mainly occurred in middle-aged and elderly people,with an average age of (58±16) years. Eosinophils were elevated in 4 patients. Immunoglobulin E (IgE) level was (530±672) kU/L in five patients. Direct immunofluorescence showed IgG and/or C3 deposition on basal membrane zone. Indirect immunofluorescence showed positive IgG anti-basement membrane zone,with a titer of 1:40-1:320. Enzyme-linked immunosorbent assay showed the anti-BP180 antibodies were positive [24-85 U/ml,average(43±26) U/ml] in 5 patients. None of the patients had neurological disorders. One patient was lost to follow-up. The disease recurred in 3 of 5 patients during the follow-up,and two patients still received maintenance corticosteroids. PN mainly occurs in middle-aged and elderly individuals. It is featured by elevated eosinophils and total IgE and relatively low anti-BP180 antibody titers. Recurrence is common but PN is less likely to be associated with neurological diseases.

Coagulation Disorders in Bullous Pemphigoid and Its Mechanism / 中国医学科学院学报

Bullous pemphigoid(BP)is an autoimmune blister disease caused by antibodies to the basement membrane zone.It usually exhibits tense bullae in skin and mucous membrane.BP patients can suffer from thrombosis due to hypercoagulation and/or hemorrhage due to the presence of anti-coagulation factors,which may be explained by the eosinophils,antibodies to the coagulation factors,and fibrinolytic system hyperactivity or inhibition.

Levels of anti-BP180 NC16A IgE do not correlate with severity of disease in the early stages of bullous pemphigoid.

Bullous pemphigoid (BP), a common autoimmune skin disease, is associated with IgG autoantibodies against the hemidesmosomal proteins, BP180 and BP230. In addition to IgG, IgE has been shown to play a role in the disease. However, the association between disease activity and IgE specific to the NC16A domain of BP180 in blister fluid remains unclear. Our objective was to evaluate the correlation between BP disease activity and BP180 NC16A-specific IgE sera and blister fluid titers, and to analyze changes during treatment. We evaluated the levels of anti-BP180 IgE autoantibodies in the sera and blister fluids of 37 BP patients using an Enzyme-linked immunosorbent assay. We also observed changes in the levels of these antibodies in 2 BP patients at 4 or 5 different time points (day 0 when the patient first visited our hospital, day 5, day 14, day 39 and day 62 for patient 1; day 0, day 4, day 8 and day 17 for patient 2). We also collected extra serum samples from the 2 patients when the disease was controlled (blister disappeared) (day 85, day 104 and day 146 for patient 1 and day 123, day 158 and day 189 for the other patient). IgE anti-BP180 antibodies were detected in the serum of 72.97 % of the patients. There was no correlation between disease activity scores and BP180 NC16A IgE titers in serum (r = -0.077, p > 0.05) or in blister fluid (r = 0.262, p > 0.05). The levels of the autoantibody in serum were positively correlated with that in blister fluid (r = 0.6651, p < 0.001); however, the levels continued to rise despite effective control of the disease in the initial two to 6 weeks of diagnosis. The level of this autoantibody reached a peak on day 39 for patient 1 and on day 17 for patient 2 although the systemic and topical medication of steroid had controlled the disease process effectively. We conclude that levels of anti-BP180 NC16A IgE are higher in the sera than blister fluids. These levels could generally reflect disease severity throughout the course of the disease, but not in the early stages of medication.

Application of cloud database in the management of clinical data of patients with skin diseases / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the needs and applications of using cloud database in the daily practice of dermatology department.</p><p><b>METHODS</b>The cloud database was established for systemic scleroderma and localized scleroderma. Paper forms were used to record the original data including personal information, pictures, specimens, blood biochemical indicators, skin lesions,and scores of self-rating scales. The results were input into the cloud database. The applications of the cloud database in the dermatology department were summarized and analyzed.</p><p><b>RESULTS</b>The personal and clinical information of 215 systemic scleroderma patients and 522 localized scleroderma patients were included and analyzed using the cloud database. The disease status,quality of life, and prognosis were obtained by statistical calculations.</p><p><b>CONCLUSIONS</b>The cloud database can efficiently and rapidly store and manage the data of patients with skin diseases. As a simple, prompt, safe, and convenient tool, it can be used in patients information management, clinical decision-making, and scientific research.</p>

Retrospective analysis of 50 cases of senile syphilis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To summarize the epidemiological features of senile syphilis.</p><p><b>METHOD</b>The clinical data of 50 elderly (>60 years) patients with syphilis who were treated in the Clinic of Sexually Transmitted Diseases of Peking Union Medical College Hospital were retrospectively analyzed.</p><p><b>RESULTS</b>There were 31 men and 19 women (male to female ratio:1.6:1). Non-marital sexual intercourse was the main route of transmission. The disease was mainly found before surgeries. Among these 50 syphilis cases, 3 were primary syphilis, 13 were secondary syphilis, 10 were early latent syphilis, 12 were late latent syphilis, and 12 were latent syphilis of unknown duration. Co-morbidities with other sexually transmitted diseases were found in 4 patients. The rate of sero-resistance was 40%.</p><p><b>CONCLUSIONS</b>The incidence of syphilis in the senile population is higher than we expected. Routine serological screening for syphilis is required in clinical settings. The underlying diseases, human hosts-related spirochetes, and laboratory testing techniques are important reasons for the false positive findings in senile patients.</p>

A new classification of nevus of Ota / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The nevus of Ota, is a common benign pigmentary dermatosis, mainly involve innervation area of first and second branch of trigeminal nerve. The classification of nevus of Ota was proposed by Tanino, based on 26 cases of nevus of Ota from 1937 to 1940. Studies about its classification are rarely seen in last 70 years, while it is still practical today.</p><p><b>METHODS</b>Based on the clinical photographs, 1079 consecutive patients with nevus of Ota were verified and reclassified according to the innervation areas of the trigeminal nerve branches.</p><p><b>RESULTS</b>In these 1079 cases, 866 patients were in line with Tanino's classification (80.26%), and 213 patients were not (19.74%). We put forward a new clinical classification (Peking Union Medical College Hospital classification, PUMCH classification) of nevus of Ota based on the innervation area of the trigeminal nerve branches, composed of 5 types and 14 subtypes. The 5 types were as follows: Type I - pigmentation maculeses involving the innervation area of one of the three trigeminal nerve branches, of which there were 424 cases (39.3%), comprising 6 subtypes; Type II - pigmentation macules involving the innervation area of two branches of the three trigeminal nerve branches, of which there were 221 cases (20.48%), comprising 4 subtypes; Type III - pigmentation macules involving the innervation area of all three trigeminal nerve branches, of which there were 361 cases (33.45%), comprising 2 subtypes; Type IV - bilateral type, in which the pigmentation macules involves the bilateral cheek, of which there were 63 cases (5.84%), comprising 2 subtypes; and Type V - complications occurred in the patient, of which there were 10 cases (0.93%).</p><p><b>CONCLUSION</b>The new classification of nevus of Ota is based on the innervation area of the trigeminal nerve branches, and it covers all types of Tanino's classifications; on that basis, some new types and subtypes are brought in and cover almost every clinical condition.</p>

Correlation between blood eosinophil level and steroid doses in patients with bullous pemphigoid / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the correlation between blood eosinophil (EOS)level and steroid doses in patients of bullous pemphigoid (BP).</p><p><b>METHODS</b>A total of 82 untreated BP inpatients (n=49) and outpatients (n=33) were enrolled in this study. The blood EOS level and the steroid doses before and after treatment were recorded. The correlation between EOS level and steroid doses was analyzed retrospectively.</p><p><b>RESULTS</b>EOS increased in 69 BP patients (84.15%); on the contrary, only 10% of normal controls had increased EOS (t=1.99,P<0.001). In 44 inpatients, the blood EOS remained high before steroid treatment, and quickly returned to normal level after the disease became stable. There was a linear correlation between EOS and steroid doses (Spearman analysis,r=0.496,P<0.001). In 5 patients who were treated by non-steroid approach, EOS level also declined after the disease was resolved.</p><p><b>CONCLUSION</b>EOS can be one of useful indicators for the application of steroids in the treatment of BP.</p>

Analysis of 1125 syphilis cases / 中国医学科学院学报

<p><b>OBJECTIVE</b>To summarize the epidemiological, clinical and serological features of syphilis.</p><p><b>METHOD</b>The clinical data of 1125 patients with syphilis were retrospectively analyzed.</p><p><b>RESULTS</b>Non-marital sexual intercourse is the main route of infection. The 129 cases of primary syphilis were featured by extragenital chancres and the 357 cases of secondary syphilis were featured by scaling macules on the palms and soles and condylomata lata. Early latent syphilis were detected in 178 cases, late latent syphilis in 174 cases, and latent syphilis of unknown duration in 285 cases. Concurrent infection with other sexually transmitted diseases were noted in 107 cases (9.51%). Most patients were treated with benzathine penicillin, and only 31 patients (2.75%) were allergic to this therapy. Except for the primary syphilis, the sensitivity of syphilis serological tests (including rapid plasma regain test, treponema pallidum particle agglutination, treponema pallidum hemagglutination assay, and fluorescent treponemal antibody-absorption) were higher than 97%.</p><p><b>CONCLUSIONS</b>The incidence of latent syphilis is high, while the incidence of late syphilis is low. Penicillin remains the treatment of choice for syphilis.</p>

Relationship between genetic polymorphisms of interferon-gamma gene intron 1 +874 site and recurrent Condyloma acuminata / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the relationship between the polymorphisms of interferon-gamma (IFN-gamma) gene intron 1 at position + 874 and Condyloma Acuminata (CA).</p><p><b>METHODS</b>IFN-gamma gene single nucleotide polymorphisms (intron 1 at position + 874) were detected in 156 subjects, including 76 patients with recurrent CA (CA group) and 80 healthy controls (control group), by polymerase chain reaction with sequence specific primers.</p><p><b>RESULTS</b>No significant difference of IFN-gamma 1 + 874 was found between CA group (TT, TA, and AA frequencies were 10.5%, 34.2%, and 55.3%, respectively) and control group (TT, TA, and AA frequencies were 7.5%, 30.0%, and 62.5%, respectively) (chi2 = 0.959, P = 0.619).</p><p><b>CONCLUSION</b>IFN-gamma gene polymorphism (intron 1 at position + 874) is not correlated with recurrent CA.</p>

Expressions of CD1a and CD83 of Langerhans cells in the local lesions of epidermodysplasia verruciformis patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the expressions of CD1a and CD83 of Langerhans cells (LC) in the lesions of epidermodysplasia verruciformis (EV) patients.</p><p><b>METHODS</b>We used immunohistochemical method to detect the expressions of CD1a and CD83 in the lesions of 10 patients with EV lesions and in the skins of 10 normal subjects.</p><p><b>RESULTS</b>No CD83 + LCs was detected in all EV patients and normal controls, but CD1a + LC was found in all cases. The quantity of CD1a + LCs in the lesions of EV patients was significantly lower than that in the normal skin (P < 0.01); furthermore, the distribution of LCs in EV lesions was uneven.</p><p><b>CONCLUSION</b>The functions of LCs may be inhibited in EV patients.</p>

Effect of neuronal differentiation induced by nerve growth factor on the tolerance-dosage of ultraviolet radiation of PC12 cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the effect of neuronal differentiation induced by nerve growth factor (NGF) on the tolerance-dosage of ultraviolet radiation of PC12 Cells.</p><p><b>METHODS</b>Neuron-differentiated PC12 cells and untreated PC12 cells were exposed to different ultraviolet radiation dosage of 10, 30, 60, 80, 100, and 200 mJ/cm2. Cell survival rates were determined by MTT assay.</p><p><b>RESULTS</b>Neuron-differentiated PC12 cells had increased tolerance dose to ultraviolet radiation with noticeable apoptosis at the radiation dose of 100 mJ/cm2 in contrast to 30 mJ/cm2 for normal PC12 cells.</p><p><b>CONCLUSION</b>Neuronal differentiation exerts the effect of increasing the tolerance dose of PC12 cells to ultraviolet radiation.</p>

Efficacy and safety of 308 nm excimer laser for vitiligo / 中国医学科学院学报

<p><b>OBJECTIVE</b>To assess the efficacy and safety of the 308 nm excimer laser for the treatment of vitiligo.</p><p><b>METHODS</b>We treated 170 patients with stable vitiligo by using the 308 nm excimer laser. The lesions of vitiligo were treated one to two times per week for 10-30 times. Efficacies were evaluated every 7 days and 3 days after the treatments were completed. Patients were followed up for two months.</p><p><b>RESULTS</b>The rates of "remarkably improved" and "cured" were 67.97% and 32.03% in faces, 54.55% and 27.27% in necks, 63.26% and 26.53% in trunks, 38.84% and 15.70% in limbs, and 0 and 0 in hands and feet. The areas of faces had a better response than those of necks, trunks, or limbs (P < 0.01), and the areas of trunks or limbs had better response than that of hands and feet (P < 0.01).</p><p><b>CONCLUSION</b>The 308 nm excimer laser is safe and effective in treating stable vitiligo and the efficacy varies in different lesion sites.</p>

Pathogenesis of human papillomavirus infection in patients with epidermodysplasia verruciformis / 中国医学科学院学报

Epidermodysplasia verruciformis (EV), a rare inherited disease, is believed to be associated with human papillomavirus (HPV) infection. EVER1/2 genes, dendritic cells, T lymphocytes, and the biological characteristics of HPV itself may play roles in the pathogenesis of HPV infection.

Genetic basis of systemic sclerosis / 中国医学科学院学报

Systemic sclerosis (SSc) is a connective tissue disease characterized by extensive fibrosis, vasculopathy, and activation of the immune system. Its pathogenesis and mechanisms have not been identified. Studies have shown that environmental and genetic factors are involved in the pathogenesis and development of SSc. Although the concordance for the disease among identical twins is low, concordance for antoantibodies associated with SSc and for fibroblast gene expression profiles is higher. However, the candidate-gene approach has not established clear associations between polymorphisms and SSc. Based on the involvement of SSc, the candidate gene can be screened from three groups: fibrosis, immune response, and vascular disease. This article summarizes the recent advances in these three aspects.

Relationship between CCR5 gene polymorphism and condyloma acuminata / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the relationship between CCR5 delta32 gene polymorphism and condyloma acuminata.</p><p><b>METHODS</b>We used polymerase chain reaction to amplify the CCR5 gene fragments in 60 patients with condyloma acuminata and 50 age- and sampling date-matched controls, and compared the difference of genotypes between these two groups.</p><p><b>RESULTS</b>No genotype difference was found between these two groups.</p><p><b>CONCLUSION</b>Condyloma acuminata are not associated with genetic polymorphism of CCR5 delta32 gene.</p>

Incidence of seroresistance of syphilis and its relevant factors / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the incidence of seroresistance of syphilis and analyze its relevant factors.</p><p><b>METHODS</b>The clinical data of 131 patients with syphilis were retrospectively analyzed. The incidence of seroresistance was investigated and the correlation between seroresistance and factors including age, gender, original titer, disease course, and medications were analyzed.</p><p><b>RESULTS</b>The incidence of seroresistance was not significantly different among patients with different ages and genders, but was significantly different among patients with different disease courses, antibody titers, and medications. Patients with a baseline serum rapid plasma reagin (RPR) titer of greater than 1: 8, a latent course, or a macrolide therapy history had higher incidences of seroresistance (i. e., 61%, 45.6%, and 72.7% respectively) than those who had a lower RPR titer, a primary course, or a benzathine penicillin therapy history.</p><p><b>CONCLUSION</b>Syphilis patients with a high baseline RPR titer, a latent course, and a macrolides therapy are prone to be seroresistant.</p>

Two novel STK11 mutations in three Chinese families with Peutz-Jeghers syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Peutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited disease. STK11/LKB1 gene germline mutations have been identified as responsible for PJS. In our study, we investigated the molecular basis of PJS and evaluated correlation between the STK11 mutations and the Chinese population.</p><p><b>METHODS</b>We collected three pedigrees of PJS and screened the 9 exons and their flanking intronic sequences of STK11/LKB1 gene in the probands and normal individuals in the families using polymerase chain reaction (PCR) and direct sequencing.</p><p><b>RESULTS</b>Sequencing of the STK11 gene in the probands of 3 families revealed two novel mutations (c180C-->G and c998-1002delGCAGC) in exon 1 and exon 8, respectively. The mutation of c180C-->G resulted in a premature termination codon. The other mutation, a deletion of five nucleotides (998-1002delGCAGC) in exon 8, predicted to generate a translational frameshift and a termination at codon 1070.</p><p><b>CONCLUSIONS</b>The growing number of mutations in PJS pedigrees suggests the molecular basis of PJS. STK11 gene mutation can be detected in most patients with PJS.</p>