Objective:To compare the efficacy, dosage, and safety of dupilumab combined with minocycline or with minocycline and systemic glucocorticoids (sGC) versus minocycline alone or in combination with sGC in patients with bullous pemphigoid (BP) .Methods:A retrospective cohort study was conducted on BP patients who visited the Department of Dermatology, Peking University First Hospital from March 2021 to June 2022 and were treated with one of the following two therapeutic regimens: minocycline alone or in combination with sGC (M-MG group), and dupilumab combined with minocycline or with minocycline and sGC (MD-MGD group). Disease control rates, time to disease control, complete remission rates, time to complete remission, BP disease area index (BPDAI) scores, drug usage, time to pruritus relief, relapse rates, and occurrence rates of adverse reactions were compared between the two groups. Survival analysis was performed using Kaplan-Meier (KM) curves and Log-rank test. Confounders were controlled by 1∶1 matching on the propensity score in the two groups.Results:A total of 164 patients were collected, including 110 in the M-MG group (62 males and 48 females, aged 74.6 ± 12.8 years) and 54 in the MD-MGD group (33 males and 21 females, aged 74.6 ± 13.3 years). After two-week follow-up, there was no significant difference in the disease control rate between the two groups ( P = 0.341); however, the minocycline dose, proportion of patients using sGC, sGC dose, and cumulative sGC dose were all significantly higher in the M-MG group than in the MD-MGD group (all P < 0.05). A total of 152 patients (92.7%) achieved disease control in the two groups during the follow-up, while the disease control rate and time to disease control did not differ between the two groups (both P > 0.05); 52 patients (31.7%) achieved complete remission, there was no significant difference in the complete remission rate between the MD-MGD group (16/54, 29.6%) and M-MG group (36/110, 32.7%; χ2 = 0.16, P = 0.689), but the time to complete remission ( M[ Q1, Q3]) was significantly shorter in the MD-MGD group (98.5[78.0, 185.2] days) than in the M-MG group (223.5 [175.2, 277.0] days, P = 0.001). KM survival curve analysis showed that the cumulative complete remission rate was significantly higher in the MD-MGD group than in the M-MG group ( P = 0.024). A total of 73 patients (44.5%) recorded the time to pruritus relief during the follow-up, and the MD-MGD group showed significantly shorter time to pruritus relief (54 patients, 14.0 [3.0, 14.0] days) compared with the M-MG group (19 patients, 14.0 [7.0, 19.0] days; P = 0.015). After propensity score matching, each group included 42 patients; during the follow-up, there was no significant difference in the complete remission rate between the M-MG group and MD-MGD group ( P > 0.05), but the time to complete remission was significantly longer in the M-MG group than in the MD-MGD group ( P = 0.019); KM survival curve analysis showed that the cumulative complete remission rate was significantly higher in the MD-MGD group than in the M-MG group ( P = 0.041). Among the 164 patients, adverse reactions occurred in 58 (35.4%), grade 3 or more severe adverse reactions occurred in 11 (6.70%), but no dupilumab-related adverse reactions were reported. Conclusions:Compared with minocycline alone or in combination with sGC in the treatment of BP, the dupilumab combination therapy could relieve pruritus and result in complete remission in a shorter time. Additionally, dupilumab could help to accelerate the reduction in dosages of sGC and minocycline, with few adverse reactions and favorable safety.

Objective:To analyze the short- and medium-term efficacy, factors influencing the efficacy, and safety of dupilumab alone or in combination for the treatment of bullous pemphigoid (BP) .Methods:A single-center retrospective cohort study was conducted. Clinical data were collected from adult BP patients, who were regularly followed up and treated with dupilumab at the Department of Dermatology, Peking University First Hospital between March 2021 and June 2022. Dupilumab was administered subcutaneously every 2 weeks at a dose of 300 mg (except for the initial dose being 600 mg). Previous medications included glucocorticoids, minocycline, immunosuppressants, etc., and their dose remained unchanged or decreased according to patient condition. The short- and medium-term response rates were evaluated at weeks 2 and 16 after the first injection of dupilumab, respectively. Multivariate logistic regression analysis was conducted to identify factors influencing the disease control rate at week 2, and odds ratios ( ORs) were calculated; a multivariate Cox regression model was employed to analyze factors influencing the disease control rate within 16 weeks of follow-up, and hazard ratios ( HRs) were calculated; multiple linear regression analysis was performed to determine factors associated with the time to pruritus relief. Results:A total of 104 BP patients were eligible, including 60 males and 44 females; they were aged 75.6 ± 12.8 years, and the disease duration ( M [ Q1, Q3]) was 4.0 (2.0, 17.0) months. According to the percentage of the lesion area to the total body surface area, the disease severity was graded, and there were 17 mild cases, 30 moderate cases, 31 severe cases, and 26 extremely severe cases; 56 patients (53.9%) were treated with dupilumab combined with oral glucocorticoids at doses of 20.0 (15.0, 30.0) mg/d. At week 2 after the start of treatment, 63 patients (60.6%) achieved disease control, and 37 (35.6%) achieved marked disease control, resulting in a short-term response rate of 96.2%. Fifty-five patients were followed up for 16 weeks, 54 (98.2%) achieved improvement, and the systemic glucocorticoid dose was reduced to 10.0 (10.0, 17.5) mg/d. Disease control was achieved in 92 of 104 patients (88.5%) within 16 weeks, with the time to disease control being 14.0 (13.0, 26.0) days and the time to pruritus relief being 12.0 (3.0, 14.0) days. Multivariate logistic regression analysis showed that the higher the baseline disease severity, the lower the disease control rate at week 2 (compared with extremely severe cases, mild cases: OR = 37.655, 95% CI: 3.664, 386.981; moderate cases: OR = 12.143, 95% CI: 2.609, 56.528; severe cases: OR = 4.014, 95% CI: 1.121, 14.369, all P < 0.05). Multivariate Cox regression analysis showed that compared with severe BP patients, mild ( HR = 2.478, 95% CI: 1.200, 5.114, P = 0.014) and moderate BP patients ( HR = 2.076, 95% CI: 1.067, 4.038, P = 0.031) were more likely to achieve disease control during the 16-week treatment and follow-up. Multiple linear regression analysis revealed that the disease duration significantly influenced the time to pruritus relief ( P = 0.006), and the longer the disease duration, the longer the time to pruritus relief. During the follow-up, 13 adverse events occurred in 11 patients (10.6%), including 6 with pulmonary infections, 2 with heart failures, 1 with scabies, 1 with viral conjunctivitis, 1 with pericardial effusion (with a high likelihood of idiopathic pericarditis), 1 with organ failure, and 1 with intracerebral hemorrhage, but none of them were clearly related to dupilumab and most of them did not affect the treatment continuation; 3 deaths were reported, including 2 due to organ failures and 1 due to lung infection, which were all unrelated to dupilumab as determined by specialists. Conclusion:Dupilumab combination therapy for BP could result in rapid disease control, relieve pruritus, and reduce systemic glucocorticoid dosage, with a good safety profile.

Abstract： Objective　To retrospectively analyze the investigation and disposal of the COVID-19 outbreak caused by the transmission of the Omicron variant in infected imported cases, and provide basis for COVID-19 outbreak management. Methods　The description epidemiological method was used to describe the COVID-19 outbreak in Sanya City from March 31 to April 15, 2022. The propagation chain was mapped and the experience gained and shortcomings identified in emergency responses were analyzed. Results　The outbreak resulted in 95 reported locally transmitted COVID-19 cases with a incubation period M(P25, P75) of 4 (3, 5) d. In the 95 cases, the proportion of cases detected through close contact screening, centralized isolation, community screening, control area screening, active treatment (examination), and key population screening were 33.68%, 22.11%, 18.95%, 12.63%, 6.32%, 4.21% and 2.11%, respectively. The epidemic spread for 6 generations, causing 5 clusters of outbreaks and 12 cases of cluster disease. The epidemic affected 12 villages/neighborhood committees, 1 bar, 1 hospital, 1 small clinic, 1 farmer's market, 1 large shopping mall and 1 restaurant in 2 districts of Sanya City. The result of gene sequencing was Omicron variant BA.1.1. Through the immediate launch of emergency plans, nucleic acid and antigen testing, controlling close contact between infected persons and close contacts, suspending indoor business sites, central urban control, and temporary suspension, COVID-19 was controlled within 16 days. Conclusions　The transmission chain of this outbreak was clear and was caused by imported cases. Strengthening the management of the pass, doing a good job in information sharing and docking, timely screening for cases, screening, pushing, controlling high-risk groups, and implementing comprehensive control measures, can effectively prevent the spread of the epidemic, providing a reference for the control of epidemic situations in relevant scenarios.

Objective:To investigate the efficacy and safety of minocycline alone or in combination with low-dose glucocorticoids in the treatment of pemphigus erythematosus and pemphigus herpetiformis, as well as their effect on immune indices.Methods:A retrospective study was conducted, and patients with newly diagnosed pemphigus erythematosus or pemphigus herpetiformis, who received initial treatment with minocycline alone or in combination with low-dose glucocorticoids and were followed up for more than 6 months, were collected from Department of Dermatology, Peking University First Hospital from June 2011 to June 2021. Data on patients′ condition and autoantibody levels were collected at baseline and different follow-up time points, and disease severity, diagnosis, changes in autoantibody levels and their relationships with efficacy were analyzed. The Kaplan-Meier method was used to analyze complete remission rate, and chi-square test to analyze the efficacy among patients with different disease severity or after different treatments.Results:A total of 24 patients of Han nationality were collected and followed up for a median period of 21.8 months, including 15 with pemphigus erythematosus and 9 with pemphigus herpetiformis. The male to female ratio was 1.4∶1, their median age was 68.8 years, and the median duration of disease was 22.1 months. All the 24 patients achieved disease control, and the time to disease control ( M [ Q1, Q3]) was 15.9 (12, 20.1) weeks. Twenty-three (95.8%) patients achieved complete remission, and the time to complete remission was 8.7 (6.4, 10) months. After 1-year treatment, no significant difference in the complete remission rate was observed between patients receiving minocycline monotherapy (11/13) and those receiving combination therapy with low-dose glucocorticoids (9/11, χ2 = 0.16, P = 0.692) . During the follow-up period, 2 patients (8.7%) experienced recurrence in disease control state, 1 of whom achieved complete remission at week 38 after dose adjustment, and the other achieved complete remission after half-a-year treatment with rituximab. There was no significant difference in the efficacy between patients with mild and moderate pemphigus ( χ2 = 0.28, P = 0.599) . Drug-related adverse reactions occurred in 3 cases, including 1 case of tinea corporis on the back and 2 cases of generalized hyperpigmentation of the skin and gingiva. Conclusion:Minocycline alone or in combination with low-dose glucocorticoids was effective for the treatment of mild to moderate pemphigus erythematosus and pemphigus herpetiformis without serious adverse reactions, but long-term efficacy, adverse reactions and patients′ prognosis should be re-evaluated in prospective multi-center studies with a large sample size in the future.

Objective:To retrospectively analyze the efficacy and safety of dupilumab in the treatment of bullous pemphigoid (BP) .Methods:Clinical data were collected from BP patients who received injections of dupilumab at an initial dose of 600 mg followed by an every-2-week regimen at a dose of 300 mg (the frequency of injections could be increased if necessary) in Department of Dermatology, Peking University First Hospital from October 2020 to October 2021, and their clinical manifestations and changes in laboratory indices were analyzed.Results:A total of 21 BP patients treated with dupilumab were included in this study. Nineteen (90.5%) patients achieved complete or marked disease control after 2-week treatment with dupilumab; 12 patients were followed up for 16 weeks, and all maintained complete disease control at 16 weeks. All patients had a bullous pemphigoid disease area index (BPDAI) score of 122.5 ± 51.1 points at baseline, which decreased to 30.6 ± 27.4 points after 2-week treatment with dupilumab ( t = 8.53, P < 0.001) , and continued to decrease to 12.7 ± 9.1 points after 4-week treatment ( t = 9.73, P < 0.001) . Pruritus was markedly relieved in all the 21 patients within 4-week treatment with dupilumab. Among 10 patients with elevated eosinophil counts at baseline, the eosinophil counts markedly decreased in 9 after treatment. The serum IgE level was elevated in 7 patients at baseline, which markedly decreased in 6 after treatment. Viral conjunctivitis occurred in 1 (4.8%) patient, and no adverse reactions were observed in other patients. Conclusion:Dupilumab is effective in the control of BP and relief of pruritus, with a favorable safety profile.

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 assess the long-term effectiveness and safety of rituximab (RTX) for the treatment of pemphigus, and to evaluate the effect of RTX on immune indices.Methods:A retrospective study was conducted, and patients with pemphigus who received monotherapy or combination therapy with RTX (375 mg/m 2 body surface area, once a week for 4 consecutive weeks) were collected from the Department of Dermatology, Peking University First Hospital from February 2008 to July 2017. Levels of autoantibodies and proportion of B cells in patients were determined at baseline and different follow-up time points, and their changes and relationship with therapeutic effect were analyzed. Time-to-event outcomes (disease control, complete remission and relapse) were estimated using the Kaplan-Meier method. The median ( M) as well as 25th ( P25) and 75th ( P75) percentile values were calculated for repeatedly measured immune indices (autoantibodies and B cells) , and the median level of immune indice-time curve was drawn. Results:A total of 53 patients of Han nationality with pemphigus were included, including 40 with pemphigus vulgaris and 13 with pemphigus foliaceus. The male to female ratio was 0.96∶1, the median age was 37.4 years, and the median duration of disease was 13.4 months at baseline. The median follow-up duration ( P25, P75) was 37.5 (25.0, 54.7) months. Forty-eight (90.6%) patients achieved disease control, and the time to disease control was 1.7 (1.1, 3.2) months. Thirty-eight (71.7%) patients achieved complete remission, and the time to complete remission was 13.1 (9.6, 27.5) months. During the follow up, 12 of the 38 (31.6%) patients who had complete remission experienced recurrence, with the time to recurrence being 12.4 (4.8, 19.8) months. The median immune indice level-time curve showed that anti-Dsg1 and Dsg3 autoantibody levels decreased when skin lesions resolved, but increased when skin lesions relapsed. The most common severe adverse reaction was pulmonary infection, with a mortality rate of 3.8% (2/53) . Conclusions:RTX shows marked long-term effectiveness for the treatment of pemphigus. Pulmonary infection during treatment is worthy of the highest attention. The autoantibody levels can serve as an index for evaluating the effectiveness of RTX in the treatment of pemphigus.

Objective: To analyze clinicopathological features of parapsoriasis. Methods: Clinical and pathological data were collected from 81 patients with parapsoriasis in Department of Dermatology, Peking University First Hospital between January 2016 and May 2018, and analyzed retrospectively. Results: Among the 81 patients with parapsoriasis, 44 were male and 37 were female, with age ranging from 6 to 77 years. Their disease course ranged from 7 days to 30 years, and the median disease course was 12 months. Moreover, 61 (75.3%) patients were aged less than 40 years, and 20 (24.7%) were aged 41 years and older. Of the 81 patients, 16 (19.8%) were diagnosed with small plaque parapsoriasis, 20 (24.7%) with large plaque parapsoriasis, 37 (45.7%) with pityriasis lichenoides chronica, and 8 (9.9%) with pityriasis lichenoides et varioliformis acuta. Additionally, distribution patterns of lesions included diffuse type in 65 cases (80.2%) , central type in 6 cases (7.4%) , and peripheral type in 10 cases (12.3%) . Histopathological examination of skin lesions revealed liquefaction degeneration of basal cells in 69 cases (85.2%) , migration of lymphocytes into the epidermis in 67 cases (82.7%) , focal parakeratosis in 42 cases (51.9%) , keratinocyte necrosis in 29 cases (35.8%) , extravasation of erythrocytes in 23 cases (28.4%) , epidermal spongiosis in 21 cases (25.9%) , and dermal perivascular focal infiltration in 61 cases (75.3%) . Conclusion Parapsoriasis has characteristic clinical and pathological manifestations, and a close combination of clinical manifestations with pathological features is necessary for its accurate diagnosis.

OBJECTIVETo study the clinicopathologic features, immunophenotype and gene rearrangement of primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL).

METHODSSeven cases of PCLBCL were enrolled into the study. Clinicopathologic analysis, immunohistochemical staining and gene rearrangement for IgH and Igκ were undertaken in the study.

RESULTSAll the seven cases were male, and the median age was 72 years. Patients usually presented with multiple purple tumors, nodules, papules and infiltrative plaques. Two patients had a history of leg injury before onset, and one had mosquito bites. Histologically, the tumor involved the dermis and subcutis with dense and diffuse infiltrative pattern composing of centroblasts and/or immunoblasts. Immunohistochemical staining showed that seven cases (7/7) expressed CD20, six (6/6) expressed bcl-2, four (4/4) expressed MUM-1, four (4/5) expressed CD79a, four (4/5) expressed PAX-5 and four (4/6) expressed bcl-6, respectively. All cases did not express CD3ε, CD45RO, CD10 and CD30. IgH gene rearranged bands were detected in three (3/6) cases and Igκ was detected in one (1/5) case. Six of the seven cases died and the remaining patient, who was 44-year-old, was alive after 22 months of follow-up.

CONCLUSIONSPCLBCL is rare, predominantly affects elderly male patients. PCLBCL has poor prognosis and high mortality, but younger patients seem to have better prognosis. Some cases had a history of trauma or mosquito bites. The relationship between the history and the onset of PCLBCL needs further evaluation.

Aged ; Aged, 80 and over ; Animals ; Antigens, CD ; analysis ; Culicidae ; Gene Rearrangement ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Immunoglobulin kappa-Chains ; genetics ; Immunophenotyping ; Insect Bites and Stings ; complications ; Leg ; Leg Injuries ; complications ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Skin Neoplasms ; genetics ; pathology

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.