DrpB (YedR) Is a Nonessential Cell Division Protein in Escherichia coli.

We report that the small Escherichia coli membrane protein DrpB (formerly YedR) is involved in cell division. We discovered DrpB in a screen for multicopy suppressors of a ΔftsEX mutation that prevents divisome assembly when cells are plated on low ionic strength medium, such as lysogeny broth without NaCl. Characterization of DrpB revealed that (i) translation initiates at an ATG annotated as codon 22 rather than the GTG annotated as codon 1, (ii) DrpB localizes to the septal ring when cells are grown in medium of low ionic strength but localization is greatly reduced in medium of high ionic strength, (iii) overproduction of DrpB in a ΔftsEX mutant background improves recruitment of the septal peptidoglycan synthase FtsI, implying multicopy suppression works by rescuing septal ring assembly, (iv) a ΔdrpB mutant divides quite normally, but a ΔdrpB ΔdedD double mutant has a strong division and viability defect, albeit only in medium of high ionic strength, and (v) DrpB homologs are found in E. coli and a few closely related enteric bacteria, but not outside this group. In sum, DrpB is a poorly conserved nonessential division protein that improves the efficiency of cytokinesis under suboptimal conditions. Proteins like DrpB are likely to be a widespread feature of the bacterial cell division apparatus, but they are easily overlooked because mutants lack obvious shape defects.IMPORTANCE A thorough understanding of bacterial cell division requires identifying and characterizing all of the proteins that participate in this process. Our discovery of DrpB brings us one step closer to this goal in E. coli.

Granuloma annulare: Clinical and histologic variants, epidemiology, and genetics.

Granuloma annulare (GA) is a poorly understood condition characterized by a set of clinical morphologic variants with 2 predominant histopathologic patterns of inflammation. This review provides a comprehensive overview of the available information about the clinical variants and histopathologic features, current epidemiologic data, and potential genetic underpinnings of GA. Much of the current understanding of GA is based on retrospective studies, case series, and case reports; this review aims to synthesize the available information and present it clearly for practicing dermatologists.

Granuloma annulare: Pathogenesis, disease associations and triggers, and therapeutic options.

Granuloma annulare (GA) represents a cutaneous reaction pattern of unknown cause with a variety of previously described potential disease associations and triggers. This review attempts to synthesize the available data regarding potential etiopathogenesis, reviews the available data on potential GA disease associations and work-up indicated for patients with GA, and discusses potential inciting triggers. In the final part, this article describes the available treatments options and supporting data, and provides a framework for approaching management of patients with GA. The previous accompanying article provided a comprehensive overview of the available information known about the clinical variants, epidemiology, genetics, and histology of GA.

Characterization of clinical photosensitivity in cutaneous lupus erythematosus.

BACKGROUND: Photosensitivity (PS) in lupus erythematosus (LE) is frequently determined by patient report. OBJECTIVE: We sought to characterize self-reported PS in cutaneous LE (CLE). METHODS: The PS survey was used to classify subject responses into 5 phenotypes: direct sun-induced CLE flare (directCLE); general exacerbation of CLE (genCLE); polymorphic light eruption-like reactions (genSkin); general pruritus/paresthesias (genRxn); and sun-induced systemic symptoms (genSys). In all, 91 subjects with CLE alone or with CLE and systemic LE were interviewed. RESULTS: In all, 81% ascribed to 1 or more PS phenotypes. CLE-specific reactions (direct sun-induced CLE flare or general exacerbation of CLE) were reported by 86% of photosensitive subjects. Higher CLE disease activity (measured by CLE Disease Area and Severity Index activity scores) was suggestive of direct sun-induced CLE flare reactions (P = .09). In all, 60% of photosensitive subjects described CLE-nonspecific reactions: polymorphic light eruption-like rash and general pruritus/paresthesias. These phenotypes often co-occurred with CLE-specific reactions and were predicted by more systemic disease activity as measured by Physicians Global Assessment (PGA) scores in regression analyses (genSkin, P = .02) and (genRxn, P = .05). In all, 36% of subjects reported systemic reactions and higher PGA scores were predictive of the sun-induced systemic symptoms phenotype (P = .02); a diagnosis of systemic LE was not (P = .14). LIMITATIONS: PS was inferred from patient report and not directly observed. CONCLUSIONS: Characterization of self-reported PS in LE reveals that patients experience combinations of CLE-specific, CLE-nonspecific, and systemic reactions to sunlight. Sun-induced CLE flares are associated with more active CLE disease. Polymorphic light eruption-like, generalized pruritus/paresthesias, and systemic reactions are associated with more active systemic disease. Recognition of PS phenotypes will permit improved definitions of clinical PS and allow for more precise investigation into its pathophysiology.

Stenotrophomonas maltophilia: an emerging multidrug-resistant opportunistic pathogen in the immunocompromised host.

Stenotrophomonas maltophilia is a multidrug-resistant opportunistic pathogen with increasing prevalence and high morbidity and mortality. In addition to its classic association with pulmonary infections, S. maltophilia can cause skin and soft tissue infections with varying clinical presentations. We describe the case of a man in his 30s with B-cell acute lymphoblastic leukaemia who presented with a solitary patch of faint but tender purpura found to have rapidly progressive S. maltophilia infection diagnosed on skin biopsy. S. maltophilia infection should be considered in the cutaneous evaluation of the immunocompromised host.

Dapsone in the management of autoimmune bullous diseases.

Dapsone is used in the treatment of autoimmune bullous diseases (AIBD), a group of disorders resulting from autoimmunity directed against basement membrane and/or intercellular adhesion molecules on cutaneous and mucosal surfaces. This review summarizes the limited published data evaluating dapsone as a therapy for AIBD.

Impact of smoking in cutaneous lupus erythematosus.

OBJECTIVE: To investigate cigarette smoking in cutaneous lupus erythematosus (CLE). DESIGN: Prospective longitudinal cohort study. SETTING: Urban cutaneous autoimmune disease clinic. PARTICIPANTS: A total of 218 individuals with CLE or systemic lupus erythematosus and lupus nonspecific skin disease seen between January 5, 2007, and July 30, 2010. MAIN OUTCOME MEASURES: Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores to assess disease severity and response to treatment and Skindex 29+3 scores to assess patient quality of life. RESULTS: Current smokers with lupus erythematosus had higher median CLASI scores (9.5) than did never (7.0) and past (6.0) smokers with CLE (P = .02). Current smokers had higher median scores on all the Skindex 29+3 subsets. Current smokers taking hydroxychloroquine sulfate had higher quinacrine hydrochloride use than did nonsmokers (P = .04). Two to 7 months after enrollment, current smokers (median CLASI change, -3) treated with only antimalarial agents improved more than never (1) and past (0) smokers (P = .02). Eight months or more after enrollment, current smokers (CLASI change, 3.5) treated with antimalarial drugs plus at least 1 additional immunomodulator improved less than never (-1.5) and past (0) smokers (P = .04). CONCLUSIONS: Current smokers with lupus erythematosus had worse disease, had worse quality of life, and were more often treated with a combination of hydroxychloroquine and quinacrine than were nonsmokers. Never and past smokers showed greater improvement when treated with antimalarial agents plus at least 1 additional immunomodulator. Current smokers had greater improvement when treated with antimalarial drugs only.

Dapsone in the management of autoimmune bullous diseases.

Dapsone is used in the treatment of autoimmune bullous diseases (AIBD), a group of disorders resulting from autoimmunity directed against basement membrane and/or intercellular adhesion molecules on cutaneous and mucosal surfaces. This review summarizes the limited published data evaluating dapsone as a therapy for AIBD.

Response to antimalarial agents in cutaneous lupus erythematosus: a prospective analysis.

OBJECTIVE: To demonstrate response to antimalarial agents in patients with cutaneous lupus erythematosus (CLE) using activity scores from the Cutaneous Lupus Erythematosus Disease Area and Severity Index, a validated outcome measure. DESIGN: Prospective, longitudinal cohort study. SETTING: University cutaneous autoimmune disease clinic. PARTICIPANTS: A total of 128 patients with CLE who presented from January 2007 to July 2010 and had at least 2 visits with activity scores. INTERVENTION: Administration of antimalarial agents. MAIN OUTCOME MEASURES: Response was defined by a 4-point or 20% decrease in activity score. Response to initiation was determined by the difference between the scores before treatment and at the first visit at least 2 months after treatment. Response to continuation was determined by the difference between the scores at the first visit and the most recent visit while undergoing treatment. RESULTS: Of 11 patients who initiated treatment with hydroxychloroquine, 55% were responders (n = 6), showing a decrease in median (interquartile range [IQR]) activity score from 8.0 (3.5-13.0) to 3.0 (1.8-7.3) (P = .03). Of 15 patients for whom hydroxychloroquine failed, 67% were responders to initiation of hydroxychloroquine-quinacrine therapy (n = 10), showing a decrease in median (IQR) activity score from 6.0 (4.8-8.3) to 3.0 (0.75-5.0) (P = .004). Nine of 21 patients who continued hydroxychloroquine treatment (43%), and 9 of 21 patients who continued hydroxychloroquine-quinacrine (43%) were responders, showing a decrease in median (IQR) activity score from 6.0 (1.5-9.5) to 1.0 (0.0-4.5) (P = .01) and 8.5 (4.25-17.5) to 5.0 (0.5-11.5) (P = .01), respectively. CONCLUSIONS: The use of quinacrine with hydroxychloroquine is associated with response in patients for whom hydroxychloroquine monotherapy fails. Further reduction in disease activity can be associated with continuation of treatment with antimalarial agents.