Case 1, a 63-year-old female patient presented with blisters and bullae arising in erythema all over the body with itching for 2 months. Two years ago, the patient underwent peri-intestinal lymph node dissection for the treatment of malignant melanoma of the rectum and anal canal, and received intravenous injection of toripalimab for preventive treatment for 1 year, and generalized skin lesions occurred 2 weeks after drug withdrawal. Direct immunofluorescence testing of erythema on the upper extremities showed that immunoglobulin G (IgG) was deposited along the basement membrane zone; salt-split indirect immunofluorescence testing of a serum sample showed liner deposition of IgG in the epidermis. Enzyme-linked immunosorbent assay (ELISA) revealed that the serum level of anti-BP180 antibodies was over 200 U/ml. The patient was diagnosed with bullous pemphigoid, but it was doubtful whether the disease was caused by PD-1 inhibitor toripalimab or not. Then, the patient received oral minocycline at a dose of 200 mg/d and prednisolone acetate at a dose of 20 mg/d, and topically applied halometasone cream all over the body. After half-a-month treatment, the blisters crusted over and the erythema darkened in color. Case 2, a 36-year-old female patient presented with generalized blisters and itching for more than 3 months. The skin lesions manifested as tense blisters, bullae, bloody bullae and crusts on the edematous erythema. The patient had a 3-year history of vaginal malignant melanoma, which was stage Ⅳ postoperative melanoma with local recurrence and lymph node metastasis nearby the right iliac vessels. After 2-year treatment with intravenous injection of toripalimab, generalized skin lesions occurred all over the body. Direct immunofluorescence testing of the erythema showed weakly positive staining for IgG, and linear deposition of IgG along the basement membrane zone; salt-split indirect immunofluorescence testing of a serum sample showed liner deposition of IgG in the epidermis. ELISA revealed that the serum level of anti-BP180 antibodies was over 200 U/ml. The case 2 was diagnosed with bullous pemphigoid, but it was also doubtful whether the disease was caused by PD-1 inhibitor toripalimab or not. Then, the case 2 was treated with oral doxycycline at a dose of 200 mg/d and oral prednisolone acetate at a dose of 40 mg/d. After 2-week treatment, the blisters completely crusted over and erythema darkened in color.

Objective To analyze the clinical features and treatment of 68 cases of mucous membrane pemphigoid (MMP).Methods Clinical data were collected from 68 patients with MMP at the Department of Dermatology,Peking University First Hospital,between August 1987 and October 2012.Skin manifestations,histopathological and immunological findings were studied,with an emphasis on treatment regimens.Results The two most frequently involved sites were oral (67/68,98.5％) and conjunctival (23/68,33.8％) mucosa in patients with MMP.Immunological examinations included direct immunofluorescence test,indirect immunofluorescence test and enzyme-linked immunosorbent assay,with a positivity rate of 50％ (8/16),20.5％ (8/39) and 53.7％ (22/41) respectively.According to lesion distribution and disease severity,patients were given local therapy (n =5) or low to moderate dose of glucocorticoids (n =55,0.4-0.5 mg/kg or 30 mg per day).The condition was controlled until the dose of glucocorticoids reached 50 mg/d in three patients with cutaneous,oral,ocular,and other mucosal involvement.The time to onset of action of glucocorticoids at the controlling dose was (11.80 ± 5.88) days,and the duration of administration of glucocorticoids at this dose varied from 0.23 to 12 months (average,3.06 ± 2.84 months).Fifteen patients were almost cured,and four patients completely cured.Of the 15 patients almost cured,the time required for a 50％ reduction in the dose of glucocorticoids was (13.29 ± 5.76) months,and that required for the control of MMP was (17.33 ± 7.71) months.The dose of glucocorticoids was decreased to 76.5％ of the controling dose at 6 months after the control of MMP,and 58.1％ of that at 12 months.Oral candidiasis occurred in three patients during the treatment.Conclusions The diagnosis of MMP is mainly based on typical clinical and histopathological findings,and current immunological examinations are insufficiently sensitive.Usually,low to moderate dose of systemic corticosteroids combined with topical therapy can lead to satisfactory treatment outcomes.

Objective To investigate the role of Castleman′s disease in the pathogenesis of paraneoplastic pemphigus (PNP). Methods In six PNP patients associated with Castleman′s disease, routine immunohistochemistry was performed on tumor tissue. Reverse transcription - PCR, DNA sequencing of cloned PCR product and in situ hybridization (ISH) were used to estimate the clonality of the B-cells in the tumors. The expression of the specific tumor B-cell clones was evaluated by Northern blot. Six patients with Castleman′s disease without mucocutaneous lesion and 3 patients with reactive lymphadenopathy were used as the controls. Results Immunohistochemistry showed that CD20-positive B-cells in high density located in lymphoid follicles. The PCR produced one discrete band of about 128 bp in every paraneoplastic pemphigus patients. After sequencing the cloned PCR product, only two kinds of highly homologous sequences were found in all of the PNP patients. The 128 bp sequences were the major clones seen in all patients, and the 122 bp sequences were the relatively minor one seen in 4 patients. Anti-sense RNA probe transcribed from a clone of 128 bp was used in ISH. Signals of ISH located in cytoplasm of the cells in follicles of the tumors. Furthermore, this probe was also used for Northern blot and showed a strong signal in PNP patients. Conclusions Castleman′s disease associated with PNP share a major B-cell clone. The B-cell clone is expressed and maybe produces functional antibody initiating the mucocutaneous immune injury.

Objective To identify features of antibodies in the supernatants of cultured Castleman's disease cells.Methods Lymphocytes of Castleman's disease were isolated and cultured.Immunofluorescence and immunoblot assays were performed with IgG extracted from culture supernatants.The immunoglobulin heavy chaingene of cultured tumor B cells was analyzed by RT-PCR,cloning and sequencing.ResultsIg Gextracted from culture supernatant scouldattachtotheepithelialcellsurfacesofmousebladdertissues.Theantibodycouldalsoidentifytwoantigencomponents,210000and190000,ofnormalhumanepidermaltis-sues.ThesequencesimilaritywasfoundinimmunoglobulinheavychaingeneofculturedtumorBcellscom-paredwiththatof6patientswithCastleman'sdiseasepreviouslyreported.Conclusions Castleman's tumor associated with paraneoplastic pemphigus can secret autoantibody with similar features to that found in patients'sera.

Objective To investigate the effects of pemphigus vulgaris (PV) on pregnancy,childbirth and neonates.Methods Clinical data were collected from 8 pregnant patients with PV who visited the Peking University First Hospital and received follow up.Results Of these patients one developed PV in the third trimester of pregnancy,and the other 7 received treatment for PV and achieved complete subsidence of mucocutaneous lesions before pregnancy.Among the 7 cases,6 were treated with prednisone ＜ 10 mg/d,and 1 was treated with prednisone 22.5 mg/d.Finally,1 patient was lost to follow-up,1 patient underwent artificial abortion on about day 40 of pregnancy with no fluctuation in disease activity.Six patients delivered a normal birth weight baby at term,of whom,1 experienced fluctuation in disease activity in mid-pregnancy,1 suffered from recurrence of PV as a result of drug withdrawal at 2 months after delivery,and the other 4 showed no changes in disease activity.Four out of six neonates were healthy,while two were born with neonatal PV and healed after topical treatment.Conclusions Safe pregnancy and delivery can be achieved in patients with PV whose condition is completely under control with lowdose glucocorticoids after withdrawal of immunosuppressive agents.Although there is a risk of PV in neonates,the prognosis is optimistic.

Objective To investigate the immunofluoresce nt and immunoblotting features of paraneoplastic pemphigus(PNP).Methods Sera were tested by indirect immunofluorecence(IIF)and immunoblotting(IB)in four patients with PNP.Results Binding of IgGand C3to the intercell ular spaces of epidermis was found in IIF with rat bladder as substrate.The titers decreased after the excision of tumo rs.The autoantibodies also bound to sub-strates of the epithelia of human ski n,rat tongue and esophagus in those p atients.The patients' sera recogni zed 210kD and 190kD antigens from human kera tinocyte extracts with IB analysis.Conclusions IIF with rat bladder as substrate can be used a screening test for PNP.PNP tends to involve epithelia of mucosa.The results of IB test m ay confirm the diagnosis of PNP of the 4p atients.[

Objective To identify the mutation of DKC1 gene and its inheritance in a pedigree with dyskeratosis congenita (DKC). Methods The mutation was detected by polymerase chain reaction(PCR)and DNA sequencing, and restriction endonuclease digestion was performed to confirm the mutation. Results A transition mutation of C to T (1058C-T) in DKC1 gene was found in the proband and his brother. This mutation results in an amino acid change from alanine to valine (A353V) in dyskerin protein. The proband′s mother and sister were carriers of this mutation gene with no phenotype of DKC. Conclusion This pedigree is an X-linked form of DKC with 1058C-T mutation in DKC1 gene.

Objective To investigate the clinical features of skin cancer.Methods Clinical data of skin cancer and precancerous skin lesions confirmed pathologically from 2005 to 2008 in Peking University First Hospital were retrospectively analyzed by using statistical methods.Results A total of 632 cases of skin cancer and precancerous skin lesions were studied.The most common skin cancer was basal cell carcinoma and squamous cell carcinoma (invasive and in situ) which accounted for 29.3%and 24.2%,respectively.The average age at onset was older than 60 years in 55.4%of the patients,between 35 and 59 years in 34.3%,younger than 35 years in 10.3%.The concordance between clinical and pathological diagnosis reached nearly 90.O%for Paget's disease,70.0% for other common skin cancer and precancerous skin lesions.Conclusions Skin cancer and precancerous skin lesions have a predilection for scalp and face.Patients aged from 35 to 59 years account for a significant proportion not only in cutaneous lymphoma but also in melanoma and epithelium-derived nonmelanoma skin cancer.

Objective To identify C0L7Al gene mutations in a family of recessive dystrophic epidermolysis bullosa (RDEB). Methods PCR and direct DNA sequencing were used to determine the mutation sites and types. PCR using allele-specific oligonucleotide primers was performed to further identify the pathogenic cause of this disease. Results The patient examined in this study was a compound heterozygote for a S48P missense mutation in exon 2 and a 3625del 11 PTC mutation in exon 27, which was a novel combination of COL7Al mutations in RDEB. Conclusion The missense mutation and the nonsense mutation in COL7Al gene are underlying causes of the Hallopeau-Siemens variant of RDEB.

0.05).No serious adverse events were reported in these two groups.The incidences of adverse event of mizolastine and loratadine were28.6%and25.5%respectively,there were no statistically significant difference between two groups(? 2 =0.25,P=0.62).Conclusions The efficacy of mizolastine and loratadine is similar in the treatment of CIU,but mizolastine is quicker in action than loratadine.The incidences of adverse events are not different in the two groups.