Rituximab in Subepidermal Blistering Diseases.

BACKGROUND: Although rituximab is known to be effective in the treatment of pemphigus, its role in subepidermal autoimmune blistering diseases is unclear and currently limited to off-label use. SUMMARY: This is a meta-analysis of case reports, case series, and retrospective studies on the effectiveness and safety of rituximab in bullous pemphigoid, mucous membrane pemphigoid, ocular pemphigoid, and epidermolysis bullosa acquisita. We compared remission and relapse rates in patients who received rituximab with those who only received conventional medical therapy. Comparisons were also made among disease subgroups. KEY MESSAGE: The present analysis suggests that patients with subepidermal autoimmune blistering diseases treated with rituximab achieve a higher rate of complete remission and encounter their first relapse after a longer time interval. However, time to remission and total relapse rates were similar between groups. Adverse events and mortality rates were no more common in patients who received rituximab. This analysis was limited by the absence of randomized controlled trials and the observation that rituximab was used as a late rescue therapy in most reports. In conclusion, rituximab may be effective in subepidermal blistering disease, but randomized controlled studies are required for the validation of current observational data.

Incidence of cutaneous graft-versus-host disease in a Singapore academic medical centre - A retrospective cohort study.

BACKGROUND: Cutaneous graft-versus-host disease (GVHD) is common in allogeneic haematopoietic stem cell transplantation. HLA mismatch is the most significant determinant of GVHD. Our study aimed to compare the incidence of cutaneous GVHD haploidentical (Haplo) and matched donors in an Asian population. METHODS: Retrospective cohort study of the 2015-2019 bone marrow transplant registry was conducted in a transplant centre. We compared the incidence of cutaneous GVHD in Haplo with allogeneic matched unrelated donor (MUD) and matched-sibling donor (MSD) transplant recipients. Secondary objectives include acute and chronic GVHD incidence, dermatology referrals, and histological findings. RESULTS: One hundred and seventy-nine out of 203 cases were reviewed; 17 (9.5%) Haplo, 80 (44.7%) MUDs and 82 (45.8%) MSDs. The median follow-up for Haplo, MUD and MSD was 15.2, 34.2 and 35.7 months, respectively. Haplo had a higher cumulative incidence of cutaneous GVHD than MUD and MSD (p = 0.053). Chronic GVHD was only reported in MSD. The most common histology was vacuolar interface changes (13 [44.8%]) with a wide range of onset post-transplant (19-456 days). CONCLUSIONS: Haplo donors may have a higher GVHD incidence than MUD and MSD in our predominantly Asian cohort. This information may be helpful when counselling patients pre-transplant. Further prospective studies are required.

Mycoplasma-induced Stevens-Johnson syndrome/toxic epidermal necrolysis: Case-control analysis of a cohort managed in a specialized center.

BACKGROUND: Mycoplasma pneumoniae (MP) infection is associated with extrapulmonary complications such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). OBJECTIVE: We evaluated the differences in epidemiology, clinical characteristics, and disease outcomes between drug-induced and Mycoplasma-related SJS/TEN. METHODS: All patients with SJS/TEN admitted to our center between 2003 and 2016 inclusive were treated under a standardized protocol. Comparative analysis was made between patients who tested positive for MP versus a control group with negative MP serology in the presence of high-notoriety drugs defined by an algorithm for assessment of drug causality in epidermal necrolysis >5. RESULTS: Of 180 cases of SJS/TEN patients treated in our institution, 6 had positive MP serologies and were compared to a control group of 71 cases of drug-induced SJS/TEN with an algorithm for assessment of drug causality in epidermal necrolysis score of >5. There were no significant differences in baseline characteristics, disease classification, body surface area involved, and extent of mucosal involvement. We found significant differences in mortality rates between the Mycoplasma and control groups on discharge (0% vs 22.5%, P < .001) and at 1-year follow up (0% vs 32.4%, P = .002), respectively. LIMITATIONS: Retrospective design, small sample size. CONCLUSION: Although recent studies have shown that MP-induced SJS/TEN is morphologically different and deserves a separate classification system, this would need to be borne out in larger prospective studies.

Pilot study of a customized nanotextile wet garment treatment on moderate and severe atopic dermatitis: A randomized clinical trial.

BACKGROUND: Atopic dermatitis (AD) is a common dermatosis. The cornerstone of eczema management is to repair and maintain skin barrier and hydration, as well as to reduce inflammation. Wet wrap therapy (WWT) is a widely used adjunct to achieve this. The conventional material used for WWT is viscose, which presents drawbacks including discomfort, high cost, and poor durability. Here, we explore the possibility of using customized nanotextile (nanopolyester) for WWT, hoping to prove that this material is non-inferior to viscose in clinical effectiveness and patient acceptance. METHODS: Patients aged 0-18 years with moderate to severe eczema were randomized to receive either viscose (Tubifast™) or nanotextile for WWT. Patients were instructed to apply WWT daily overnight for 2 weeks. Patients' disease severity score (IGA, SCORAD) and quality of life (QoL) score (IDQOL/CDLQI) were measured on day 0, 7, and 14 of treatment. Patient survey was conducted to collect patients' feedback about garment use. RESULTS: Fifty-three children aged 7 months to 17 years were recruited (27 in Tubifast™ and 26 in nanotextile group). Patients in both groups showed significant improvement in disease severity and QoL from baseline (P < .001), and such improvement was similar in both groups. However, nanotextile garment was significantly more comfortable (2.73/10 vs 5.12/10, P = .001), easier to wear (2.78/10 vs 5.24/10, P = .003), and cooler (2.43/10 vs 3.96/10, P = .033) from patients' feedback. CONCLUSION: This study demonstrates that nanomaterial is as effective as conventional viscose in WWT, while superior in patient acceptability. Nanotextile for WWT has good potential in eczema management, especially in patients with suboptimal response to topicals alone.

Risk factors and diagnostic markers of bacteremia in Stevens-Johnson syndrome and toxic epidermal necrolysis: A cohort study of 176 patients.

BACKGROUND: Sepsis is the main cause of death in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVES: Our aim was to identify admission risk factors predictive of bacteremia and the accompanying clinical or biochemical markers associated with positive blood cultures. METHODS: A retrospective cohort study over a 14-year period (2003-2016) was performed. RESULTS: The study included 176 patients with SJS (n = 59), SJS-TEN overlap (n = 51), and TEN (n = 66). During hospitalization, bacteremia developed in 52 patients (29.5%), who experienced poorer outcomes, including higher intensive care unit admission (P < .0005), longer length of stay (P < .0005), and higher mortality (P < .0005). There were 112 episodes of bacteremia, and isolates included Acinetobacter baumannii (27.7%, n = 31) and Staphylococcus aureus (21.4%, n = 24). On multivariate analysis, clinical factors present at admission that were predictive of bacteremia included hemoglobin ≤10 g/dL (odds ratio [OR] 2.4, confidence interval [CI] 2.2-2.6), existing cardiovascular disease (OR 2.10, CI 2.0-2.3), and body surface area involvement ≥10% (OR 14.3, CI 13.4-15.2). The Bacteremia Risk Score was constructed with good calibration. Hypothermia (P = .03) and procalcitonin ≥1 µg/L (P = .02) concurrent with blood culture sampling were predictive of blood culture positivity. LIMITATIONS: This is a retrospective study performed in a reference center. CONCLUSION: Hemoglobin ≤10 g/dL, cardiovascular disease, and body surface area involvement ≥10% on admission were risk factors for bacteremia. Hypothermia and elevated procalcitonin are useful markers for the timely detection of bacteremia.

Cyclosporine treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis: Retrospective analysis of a cohort treated in a specialized referral center.

BACKGROUND: Treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) remains controversial. OBJECTIVE: We sought to evaluate the impact of cyclosporine on hospital mortality in patients with SJS/TEN. METHODS: All patients with SJS and TEN admitted to our center from 2011 to 2014 were treated under a standardized protocol that allowed for cyclosporine therapy if the inclusion and exclusion criteria were met. Clinical data were reviewed retrospectively. Comparative analysis was made on mortality outcomes with patients treated with cyclosporine versus what was expected based on SCORTEN. RESULTS: In all, 44 patients were admitted during the study period. A total of 24 patients received cyclosporine and the remaining 20 patients were treated supportively. SCORTEN predicted 7.2 deaths and 3 were observed in the group treated with cyclosporine. In the group treated supportively, SCORTEN predicted 5.9 deaths and 6 deaths were observed. The standardized mortality ratio of SJS/TEN treated with cyclosporine was 0.42 (95% confidence interval 0.09-1.22). LIMITATION: Small sample size, retrospective design, and referral bias are limitations. CONCLUSION: The use of cyclosporine may improve mortality in SJS/TEN and needs to be validated in controlled studies.

Cutaneous Presentation of Angioimmunoblastic T-Cell Lymphoma: A Harbinger of Poor Prognosis?

A 62-year-old woman presented with a 2-year history of extensive, pruritic dermatosis over her face, trunk, and limbs. She was initially treated for psoriasis with methotrexate 5 mg twice weekly and topical clobetasol cream; however, her condition worsened, and she was admitted for generalized exfoliative dermatitis. Examination showed generalized erythema and scaling affecting her face (Figure 1A), chest (Figure 1B), back, and limbs. There were also cervical, axillary, and inguinal lymphadenopathy. Laboratory studies revealed a high white blood cell count of 125×109/L (reference range: 4-10×109/L), hemoglobin level of 11.9 g/dL (reference range: 12-16 g/dL), and normal platelet level of 396×109/L (reference range: 140-440×109/L). Results from direct Coombs test were negative and lactate dehydrogenase levels were normal.

Cellulitis Recurrence Score: a tool for predicting recurrence of lower limb cellulitis.

BACKGROUND: Cellulitis is the most common skin and soft tissue infection and is associated with frequent recurrences. OBJECTIVES: An objective of our study was to identify factors for recurrence in patients who present with a first episode of lower-limb cellulitis. A secondary aim was to formulate a score based on observed clinical risk factors that might predict recurrence within a year. METHODS: Dermatology referral forms and national computerized records were reviewed from 2003 to 2012. Demographics, coexistent dermatoses, local factors, and comorbidities were reviewed. RESULTS: A total of 102 (45.3%) of 225 patients had recurrence. Multivariate analysis showed that lymphedema (P < .0005), chronic venous insufficiency (P < .0005), peripheral vascular disease (P = .002), and deep vein thrombosis (P = .008) predicted for recurrence. The Cellulitis Recurrence Score (CRS) was constructed based on these factors. CRS ≥ 2 was associated with a positive predictive value of 83.6% and negative predictive value of 67.5%. Model performance was good (Hosmer-Lemeshow statistic, P = .753). LIMITATIONS: This is a retrospective study limited to an inpatient cohort. CONCLUSION: Lymphedema, chronic venous insufficiency, peripheral vascular disease, and deep vein thrombosis were risk factors. CRS is reliable for predicting recurrence, and early interventions should be considered in patients with CRS ≥ 2.

Infectious complications in bullous pemphigoid: an analysis of risk factors.

BACKGROUND: Infections are common in bullous pemphigoid and contribute to significant mortality. OBJECTIVES: We sought to define the spectrum of infectious complications and to identify associated risk factors in a bullous pemphigoid cohort. DESIGN: A retrospective cohort study conducted at an academic medical center. RESULTS: In all, 97 patients were included. Infectious complications occurred in 54 patients (56%) and the median duration from diagnosis to first episode of infection was 3 months. Bacteremia occurred in 14 patients (26%) and 26 of 30 deaths (87%) were attributable to infections. On univariate analysis, significant risk factors include low Karnofsky score (<60) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.5-8.3; P < .01), high Charlson comorbidity index score (≥6) (OR 2.4, 95% CI 1.1-5.5; P = .04), and dementia (OR 4.9, 95% CI 1.5-15.8; P = .01). On multivariate analysis, low Karnofsky score and dementia remained significant with an OR of 3.3 (95% CI 1.1-10.0; P = .03) and OR of 4.2 (95% CI 1.2-14.7; P = .03), respectively. LIMITATIONS: Limitations include potential selection bias as a result of study design and primary outcome measures focused on significant infections requiring hospitalizations. Minor infections were not included. CONCLUSIONS: Identified risk factors for infectious complications include functional impairment and the presence of dementia, which may allow for better risk stratification and individualized treatment of bullous pemphigoid.

Management of Adult Patients With Drug Reaction With Eosinophilia and Systemic Symptoms: A Delphi-Based International Consensus.

Importance: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. To our knowledge, there is no international consensus on its severity assessment and treatment. Objective: To reach an international, Delphi-based multinational expert consensus on the diagnostic workup, severity assessment, and treatment of patients with DRESS. Design, Setting, and Participants: The Delphi method was used to assess 100 statements related to baseline workup, evaluation of severity, acute phase, and postacute management of DRESS. Fifty-seven international experts in DRESS were invited, and 54 participated in the survey, which took place from July to September 2022. Main Outcomes/Measures: The degree of agreement was calculated with the RAND-UCLA Appropriateness Method. Consensus was defined as a statement with a median appropriateness value of 7 or higher (appropriate) and a disagreement index of lower than 1. Results: In the first Delphi round, consensus was reached on 82 statements. Thirteen statements were revised and assessed in a second round. A consensus was reached for 93 statements overall. The experts agreed on a set of basic diagnostic workup procedures as well as severity- and organ-specific further investigations. They reached a consensus on severity assessment (mild, moderate, and severe) based on the extent of liver, kidney, and blood involvement and the damage of other organs. The panel agreed on the main lines of DRESS management according to these severity grades. General recommendations were generated on the postacute phase follow-up of patients with DRESS and the allergological workup. Conclusions and Relevance: This Delphi exercise represents, to our knowledge, the first international expert consensus on diagnostic workup, severity assessment, and management of DRESS. This should support clinicians in the diagnosis and management of DRESS and constitute the basis for development of future guidelines.

Cytokines and chemokines in irritant contact dermatitis.

Irritant contact dermatitis is a result of activated innate immune response to various external stimuli and consists of complex interplay which involves skin barrier disruption, cellular changes, and release of proinflammatory mediators. In this review, we will focus on key cytokines and chemokines involved in the pathogenesis of irritant contact dermatitis and also contrast the differences between allergic contact dermatitis and irritant contact dermatitis.

Allopurinol non-covalently facilitates binding of unconventional peptides to HLA-B*58:01.

Allopurinol, widely used in gout treatment, is the most common cause of severe cutaneous adverse drug reactions. The risk of developing such life-threatening reactions is increased particularly for HLA-B*58:01 positive individuals. However the mechanism of action between allopurinol and HLA remains unknown. We demonstrate here that a Lamin A/C peptide KAGQVVTI which is unable to bind HLA-B*58:01 on its own, is enabled to form a stable peptide-HLA complex only in the presence of allopurinol. Crystal structure analysis reveal that allopurinol non-covalently facilitated KAGQVVTI to adopt an unusual binding conformation, whereby the C-terminal isoleucine does not engage as a PΩ that typically fit deeply in the binding F-pocket. A similar observation, though to a lesser degree was seen with oxypurinol. Presentation of unconventional peptides by HLA-B*58:01 aided by allopurinol contributes to our fundamental understanding of drug-HLA interactions. The binding of peptides from endogenously available proteins such as self-protein lamin A/C and viral protein EBNA3B suggest that aberrant loading of unconventional peptides in the presence of allopurinol or oxypurinol may be able to trigger anti-self reactions that can lead to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).