Lid Margin Microbiome in Stevens-Johnson Syndrome Patients With Lid Margin Keratinization and Severe Dry Eye Disease.

Purpose: The current study evaluated the lid margin microbiome of keratinized lid margins of patients with chronic Stevens-Johnson syndrome (SJS) and compared it with healthy controls and historically reported lid margin microbiome of patients with meibomian gland dysfunction (MGD). Methods: Eyelid margin swabs of 20 asymptomatic adults (mean age = 29 ± 12 years) and 10 patients with chronic SJS (mean age = 31.2 ± 14 years) with lid margin keratinization were sequenced using next generation of 16S rDNA V3 to V4 variable region. Within SJS, the keratinized lid margin microbiome was compared with adjacent eyelid skin. Results: All patients had obstructive MGD, and mean Schirmer I value was 2.8 ± 1.9 mm. The phyla were similar in two groups, whereas at the genera level, an increase in the relative abundance of Corynebacterium, Haemophilus, Azotobacter, and Afipia and a decrease of Acinetobacter was noted in SJS compared to healthy lid margins. SJS-associated microbiota displayed lesser diversity and more heterogeneity than healthy controls. The Principal Components Analysis (PCA) plot revealed wide separation in the SJS and the control groups. Correlational network analysis revealed Corynebacterium and Sphingomonas forming a major hub of negative interactions with other bacterial genera in the SJS group. Significant differences exist in the prevalent genera between keratinized lid margins and historically reported meibum microbiome of patients with MGD. In addition, the eyelid skin of patients with SJS had predominant Staphylococcus, whereas Corynebacterium and Pseudomonas were more in the keratinized lid margins compared to the eyelid skin microbiome. Conclusions: Lid margin microbiome is significantly altered in the keratinized lid margins of patients with SJS compared to the eyelid skin of patients with SJS, normal lid margins, and patients with MGD.

Diphtheroids as Corneal Pathogens in Chronic Ocular Surface Disease in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

PURPOSE: To characterize diphtheroid corneal infections in eyes in the chronic phase of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Observational case series. RESULTS: Four eyes of 3 patients were included in this review. Each eye presented with persistent corneal epithelial defect with corneal thinning in the chronic phase of SJS/TEN. None of the epithelial defects were associated with stromal infiltration. The corneas were cultured at the time of workup of persistent epithelial defect (3 eyes) or at time of tectonic penetrating keratoplasty after perforation (1 eye). Cultures yielded abundant growth of Corynebacterium spp., including Corynebacterium jeikeium (n = 2), Corynebacterium glucuronolyticum (n = 1), and a multidrug-resistant Corynebacterium striatum isolate (n = 1). The ocular surface was stabilized with surgical intervention (1 eye) or with introduction of fortified topical antibiotic based on laboratory identification and susceptibility testing of the isolated organisms (3 eyes). Numerous risk factors for microbial keratitis were present in all 4 eyes. CONCLUSIONS: In eyes with a persistent corneal epithelial defect in the chronic phase of SJS/TEN, even in the absence of an infiltrate, corneal culture should be undertaken. Recognition and treatment of Corynebacterium spp. as opportunistic pathogens may lead to favorable outcomes in cases of clinically sterile ulceration during the chronic phase of SJS/TEN.

Reactive infectious mucocutaneous eruption: Mycoplasma pneumoniae-induced rash and mucositis and other parainfectious eruptions.

Mycoplasma pneumoniae-induced rash and mucositis is the most accurate diagnosis for patients with blistering mucocutaneous disease provoked by an infection. Recent literature suggests expansion of the name is required, as other infections have caused a clinically similar presentation. This review provides a concise update on current understanding of M. pneumoniae-induced rash and mucositis and other reactive infectious mucocutaneous eruptions.

A retrospective analysis of infections and antibiotic treatment in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare drug-related life-threatening acute conditions. Infection is a major cause of morbidity and mortality in these patients. The aim of this study was to analyze the infective characteristics and antimicrobial strategies in patients with SJS and TEN.Methods: A total of 125 patients who were diagnosed with SJS/TEN in West China Hospital from 2010 to 2017 were retrospectively analyzed.Results: There were 75 patients with coinfections (75/125, 60%), of whom 44 had SJS (44/90, 48.9%) and 31 had TEN (31/35, 88.6%). The most common infections were skin infections and pulmonary infections. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were the most frequently identified pathogenic organisms. The most common antibiotics used in patients with infections were vancomycin, carbapenems, quinolones, macrolides, and lincomycin.Conclusions: Antimicrobial therapy should be administered promptly if there are clinical signs of an infection. Empiric antibiotic selection is based on knowledge of the local microbiota, the different infected sites, the pathogens involved, and the severity of disease.

[Drug-induced toxic epidermal necrolysis with secondary aspergillus fumigatus infection: a case report].

Among the various drug induced dermatological entities toxic epidermalnecrolysis (TEN) and Stevens-Johnson syndrome (SJS) occupy a primary place in terms of mortality. Toxic epidermal necrolysis also known as Lyell's syndrome was first described by Lyell in 1956. Drugs are by far the most common cause of toxic epidermal necrolysis, in which large sheets of skin are lost from the body surface making redundant the barrier function of the skin, with its resultant complications. Drug-induced toxic epidermal necrolysis are severe adverse cutaneous drug reactions to various precipitating agents that predominantly involve the skin and mucous membranes. Toxic epidermal necrolysis is rare but considered medical emergencies as they are potentially fatal. Drugs are the most common cause accounting for about 65%-80% of the cases. The most common offending agents are sulfonamides, NSAIDs, butazones and hydrantoins. An immune mechanism is implicated in the pathogenesis, but its nature is still unclear. There is a prodormal phase in which there is burning sensation all over the skin and conjunctivae, along with skin tenderness, fever, malaise and arthralgias. Early sites of cutaneous involvement are the presternal region of the trunk and the face, but also the palms and soles, rapidly spread to their maximum extent, the oral mucosa and conjunctiva being affected. Initial lesions are macular, followed by desquamateion, or may be from atypical targets with purpuriccenters that coalesce, from bullae, then slough. The earlier a causative agent is withdrawn the better is the prognosis. Several treatment modalities given in addition to supportive care are reported in the literature, such as systemicsteroids, high-dose intravenous immunoglobulins, ciclosporin, TNF antagonists. Recovery is slow over a period of 14-28 days and relapses are frequent. Mortality is 25%-50% and half the deaths occur due to secondary infection. Here we report a 50-year-old female of drug-induced toxic epidermal necrolysis. She was admitted to the dermatology ward with extensive peeling of skin over the trunk and limbs. She had taken alamotrigine for epilepsy. A week after taking the tablets, the patient developed a severe burning sensation all over the body and followed by a polymorphic erythematous dermatitis and widespread peeling of skin. We treated this patient with high dose corticosteroids, high-dose intravenous immunoglobulins and etanercept, but eventually she died of secondary aspergillus fumigatus infection.

Microbial Keratitis in Stevens-Johnson Syndrome: A Prospective Study.

PURPOSE: To evaluate the microbiological profile and outcome in cases with infective keratitis in Stevens-Johnson syndrome (SJS). METHODS: Eighty-three eyes of 68 patients with SJS presenting with microbial keratitis were recruited and managed with standard antimicrobial therapy. RESULTS: Microbial keratitis developed in 34% of patients with SJS (83 eyes, 68 patients) over a period of 5 years. Four eyes (4.8%) had a history of concurrent topical steroid use at the onset of keratitis. Mean baseline best-corrected visual acuity was 1.8 ± 0.9 logMAR units. The site of corneal ulceration was central in 52 eyes (62.6%), paracentral in 17 eyes (20.5%), and peripheral in 14 eyes (16.8%). The mean ulcer area was 3.9 ± 2.7 mm. Approximately 15 of 24 (62.5%) culture-positive eyes had bacterial infection, most of which (80%) were caused by Gram-positive bacteria. Polymicrobial infection was noted in 7 of 24 eyes (29.1%). Although 57 of 83 (68.6%) eyes healed with medical therapy, 26 of 83 (31.3%) eyes had corneal perforation and were managed with cyanoacrylate glue application (30.7%) or therapeutic keratoplasty (69.3%). Systemic infection as an inciting factor of SJS and an early presentation for keratitis were the major risk factors associated with corneal perforation. Large mean ulcer size, paracentral ulcers, and punctal involvement were associated with a good visual outcome. CONCLUSIONS: Infective keratitis in SJS is common, and unlike routine cases, surgical intervention is often required. However, the antibiotic sensitivity pattern suggests that resistance is not that high.

Pediatric toxic epidermal necrolysis treated successfully with infliximab.

Successful management of toxic epidermal necrolysis (TEN) with tumor necrosis factor-α inhibitors has been described in adults. We present a case of a 7-year-old boy with infection-associated TEN, diagnosed by typical clinical and histopathological features, most likely caused by Mycoplasma pneumoniae. Treatment with a single dose of infliximab 5 mg/kg intravenously on day 5 after the onset of symptoms was followed by cessation of all blister formation over 3 days and complete resolution within a week. Sequelae were mild, consisting of postinflammatory hyperpigmentation and dry eyes.

Toxic epidermal necrolysis data from the CELESTE multinational registry. Part I: Epidemiology and general microbiological characteristics.

INTRODUCTION: Toxic epidermal necrolysis (TEN) is a rare, life-threatening autoimmune disease predominantly manifested in the skin and mucous membranes. Today, infectious complications have the dominant share in mortality of TEN patients. Due to the nature of the therapy and administration of immunosuppressive medications, a wide range of potentially pathogenic microorganisms, which cause infectious complications in different compartments in these patients, is not surprising. MATERIAL AND METHODOLOGY: This is a multicentric study, which included all patients with TEN hospitalized between 2000-2015 in specialized centres in the Czech Republic and Slovakia. The total catchment area was over 12.5 million inhabitants. The actual implementation of the project was carried out using data obtained from the registry CELESTE (Central European LyEll Syndrome: Therapeutic Evaluation), when specific parameters relating to epidemiological indicators and infectious complications in patients with TEN were evaluated in the form of a retrospective analysis. RESULTS: In total, 39 patients with TEN were included in the study (12 patients died, mortality was 31%), who were hospitalized in the monitored period. The median age of patients in the group was 63 years (the range was 4-83 years, the mean was 51 years), the median of the exfoliated area was 70% TBSA (total body surface area) (range 30-100%, mean 67%). SCORTEN was calculated for 38 patients on the day of admission. Its median in all patients was 3 (range 1-6; mean 3). Any kind of infectious complication in the study group was recorded in 33 patients in total (85%). In total, 30 patients (77%) were infected with gram-positive cocci, 27 patients (69%) with gram-negative rods, and yeast cells or fibrous sponge were cultivated in 12 patients (31%). A total of 32 patients (82%) were found to have infectious complications in the exfoliated area, 15 patients (39%) had lower respiratory tract infections, 18 patients (46%) urinary tract infections and 15 patients (39%) an infection in the bloodstream. The most common potentially pathogenic microorganism isolated in our study group was coagulase neg. Staphylococcus, which caused infectious complications in 24 patients. Enterococcus faecalis/faecium (19 patients), Pseudomonas aeruginosa (17 patients), Staphylococcus aureus (11 patients) and Escherichia coli (11 patients) were other most frequently isolated micro-organisms. CONCLUSION: The published data were obtained from the unique registry of TEN patients in Central Europe. In the first part, we have succeeded in defining the basic epidemiological indicators in the group of patients anonymously included in this registry. The study clearly confirms that infectious complications currently play an essential role in TEN patients, often limiting the chances of survival. The study also shows a high prevalence of these complications in the period after 15days from the start of hospitalization, when most patients already have completely regenerated skin cover.

Characterization of Children With Recurrent Episodes of Stevens Johnson Syndrome.

We performed a retrospective chart review for all cases of recurrent Stevens Johnson Syndrome (SJS) from March 2013 to March 2016. Nine children had 29 episodes of SJS or incomplete SJS; all children were male and 8 (88%) were white. Episodes affected mucus membranes with minimal skin involvement. Mycoplasma infections and HLA-B27/-B51 were common.

Microbiological findings and antibacterial therapy in Stevens-Johnson syndrome/toxic epidermal necrolysis patients from a Swedish Burn Center.

BACKGROUND: Superimposed infections/sepsis are the major cause of morbidity/mortality in Stevens-Johnson syndrome/Toxic Epidermal Necrolysis (SJS/TEN). It is a delicate balance between avoiding new pharmaceuticals and prophylactically treat an incipient infection. The objective of this study was to investigate the rates and types of infection-microbials and antibiotics involved in SJS/TEN patients. MATERIALS AND METHODS: Microbiology and clinical data were collected for SJS/TEN patients admitted to our Burn Center from January 2010 through January 2016. RESULTS: A total of 24 patients were admitted over the study period. There were 303 bacterial cultures taken whereof 113 (37.3%) were positive (median of 4.4 per patient). Twenty-two (91.7%) patients had at least 1 positive sample recorded. Fifteen (62.5%) patients had a confirmed episode of sepsis with skin being the most common source of colonization (77.8%). Eleven (45.8%) patients received empiric antibiotic therapy at referral facility/prior to admission to our Center. Patients who grew a higher number of different species were significantly less likely to have received early empiric antimicrobial therapy (P < .001). CONCLUSION: Secondary bacterial infection and sepsis were a highly common finding in our patient population. Despite the risk of resistance and further immunological provocation, empirical antibiotic treatment might have a place in clinical management.

Epidemiology and Molecular Characteristics of Mycoplasma pneumoniae During an Outbreak of M. pneumoniae-associated Stevens-Johnson Syndrome.

BACKGROUND: An increase in Mycoplasma pneumoniae-associated Stevens-Johnson syndrome (SJS) cases at a Colorado pediatric hospital led to an outbreak investigation. We describe the epidemiologic and molecular characteristics of M. pneumoniae among SJS case-patients and surrounding community members during the outbreak. METHODS: M. pneumoniae polymerase chain reaction-positive respiratory specimens from 5 Colorado hospitals and 4 referral laboratories underwent confirmatory polymerase chain reaction testing; positive specimens then underwent multilocus variable-number tandem-repeat analysis (MLVA) and macrolide resistance testing. Three SJS-M. pneumoniae case-patient households were surveyed using a standardized questionnaire, and nasopharyngeal/oropharyngeal swabs were obtained from all consenting/assenting household contacts. International Classification of Diseases, 9th revision codes were used to identify pneumonia cases among Colorado patients 5-21 years of age from January 2009 to March 2014. RESULTS: Three different M. pneumoniae MLVA types were identified among the 5 SJS case-patients with confirmed infection; MLVA type 3-X-6-2 was seen more commonly in SJS case-patients (60%) than in 69 non-SJS community specimens (29%). Macrolide resistance was identified in 7% of community specimens but not among SJS case-patients. Of 15 household contacts, 5 (33%) were M. pneumoniae positive; all MLVA types were identical to those of the corresponding SJS case-patient, although the specimen from 1 contact was macrolide resistant. Overall pneumonia cases as well as those caused by M. pneumoniae specifically peaked in October 2013, coinciding with the SJS outbreak. CONCLUSIONS: The outbreak of M. pneumoniae-associated SJS may have been associated with a community outbreak of M. pneumoniae; clinicians should be aware of the M. pneumoniae-SJS relationship. Household transmission of M. pneumoniae was common within the households investigated.

Conjunctival Microbial Flora in Ocular Stevens-Johnson Syndrome Sequelae Patients at a Tertiary Eye Care Center.

PURPOSE: To evaluate the conjunctival microbial flora in cases of ocular Stevens-Johnson Syndrome (SJS) in a tertiary eye care center. METHODS: This prospective study comprised 176 eyes of 88 patients with ocular SJS compared with 124 eyes of normal subjects. The conjunctival swabs were collected and sent for microbiological analysis for bacterial isolation and antibiotic sensitivity examination. The type of bacteria isolated and its antibiotic sensitivity pattern were studied. RESULTS: Of 176 eyes, 104 (59%) had positive cultures for bacteria in cases of SJS and 16 (12.9%) had positive culture in the control group, the difference being statistically significant (P = 0.001). In the SJS group, 14 different types of bacterial isolates were identified. The most common isolate was coagulase-negative staphylococci (CNS) (30/104, 28.8%) followed by Corynebacteria species (35/104, 33.6%) and Staphylococcus aureus (19/104, 18.2%). More than 1 bacteria were isolated in 7 eyes (6.7%). Most of the isolates showed resistance to ciprofloxacin with no resistance to gatifloxacin and moxifloxacin. In the control group, only 2 bacteria were isolated, which included CNS (14/16, 87.5%) and Streptococcus pneumoniae (2/16, 12.5%). CNS showed resistance to ciprofloxacin, and S. pneumoniae was resistant to tobramycin and gentamycin. CONCLUSIONS: Ocular SJS is associated with alteration of the normal microbial flora residing in the conjunctival sac. The study of which is vital in cases of infection in these eyes with compromised ocular surface. Mixed flora are seen more often in cases of ocular SJS as compared with controls.

Outbreak of Mycoplasma pneumoniae-Associated Stevens-Johnson Syndrome.

BACKGROUND: Stevens-Johnson syndrome (SJS) is an uncommon, sporadic disease and outbreaks are rare. In November 2013, an outbreak of SJS was identified at Children's Hospital Colorado. METHODS: Outbreak cases were children aged 5-21 with a discharge diagnosis of SJS admitted from September 1 to November 30, 2013. Medical charts were reviewed using standardized data collection forms. Respiratory specimens were tested for viruses and Mycoplasma pneumoniae (Mp) by polymerase chain reaction (PCR). We conducted a separate 4-year retrospective case-control study comparing hospitalized SJS cases with and without evidence of Mp infection. RESULTS: During the outbreak, 8 children met SJS criteria. Median age was 11.5 years (range 8-16 years); 5 (63%) were boys and 5 (63%) were Mp-PCR-positive. Of the 5 PCR-positive children, none had preceding medication exposure, and all had radiographic pneumonia. All outbreak Mp isolates were macrolide susceptible. The retrospective case-control analysis showed that Mp-associated SJS episodes (n = 17) were more likely to have pneumonia (odds ratio [OR] 7.5, confidence interval [CI] 1.6­35.1), preceding respiratory symptoms (OR 30.0, CI 3.3­269.4) [corrected] an erythrocyte sedimentation rate ≥35 mg/dL (OR 22.8, CI 2.1-244.9), and ≤3 affected skin sites (OR 4.5, CI 1.2-17.4) than non-Mp-associated SJS episodes (n = 23). CONCLUSIONS: We report the largest outbreak of SJS in children, which was also predominately associated with Mp infection. Mp-associated SJS was associated with a distinct clinical presentation that included less extensive skin disease, an elevated erythrocyte sedimentation rate, and evidence of a preceding respiratory infection.

What's new with common, uncommon and rare rashes in childhood.

PURPOSE OF REVIEW: Children with rashes account for many of the outpatient visits to a general pediatrician. As such, pediatricians are often the first to identify and treat these rashes. Establishing an approach to common, uncommon and rare pediatric rashes assists in accurate assessment. This review highlights newly identified clinical patterns and disease severity. RECENT FINDINGS: Group A ß-hemolytic streptococci (GABHS) have been shown to be an important cause of intertrigo and to cause more widespread disease in some instances. Superficial skin infections with GABHS have been associated with strains secreting exfoliating toxins, whereas deeper infections have been associated with superantigen toxins. Hand-foot-and-mouth disease (HFMD) outbreaks have occurred with more virulent strains, causing more widespread disease that may be confused with eczema herpeticum or varicella. Mycoplasma pneumoniae has been shown to be an important cause of common disorders such as urticaria, and less common disorders such as Stevens-Johnson syndrome and Mycoplasma-associated mucositis. Recurrent toxin-mediated erythema is a recently described entity that must be differentiated from Kawasaki disease. SUMMARY: The number of rashes acquired in childhood is vast, requiring the pediatrician to be able to identify worrisome rashes from those with a more benign course. Key clinical signs may assist in clinical diagnosis and treatment.

Mycoplasma-associated Stevens-Johnson syndrome in children: retrospective review of patients managed with or without intravenous immunoglobulin, systemic corticosteroids, or a combination of therapies.

Administration of intravenous immunoglobulin (IVIG) to patients with Stevens-Johnson syndrome (SJS) has been controversial. The objective of this study was to evaluate the effectiveness of IVIG, systemic corticosteroids, or both in treating Mycoplasma pneumoniae-associated SJS (mpSJS). Retrospective series of 10 pediatric mpSJS cases were stratified into four treatment groups: IVIG alone, IVIG and systemic corticosteroids together, systemic corticosteroids alone, and supportive care. The efficacy of therapy was evaluated on the basis of several proxies of disease severity, including hospital length of stay (LOSt ) and number of febrile days (Febt ) after initiation of therapy. Patients treated with IVIG alone had a longer LOSt and more Febt , despite different baseline characteristics, than patients treated with supportive therapy. Of patients who received IVIG, 50% were treated with corticosteroids concurrently and had similar characteristics of disease severity but showed a non-statistically significant trend toward shorter LOSt and fewer Febt than those who received IVIG alone. A patient treated with corticosteroids alone had the shortest LOSt in this series. Therefore treatment with IVIG alone was associated with a more severe disease course than supportive therapy, although causality cannot be inferred given possible confounding by indication. When systemic corticosteroids were used alone or in conjunction with IVIG, hospital LOSt and Febt trended lower than with the use of IVIG alone, although disease severity at baseline was similar between those treated with IVIG and corticosteroids concurrently and those treated with IVIG alone. It was thus concluded that treatment with systemic corticosteroids as monotherapy or in combination with IVIG may be preferable to IVIG alone. Further large-scale studies are warranted to evaluate this hypothesis.

Mycoplasma pneumonia--associated mucocutaneous disease in children: dilemmas in classification.

There is controversy regarding precise definitions for Stevens-Johnson syndrome (SJS) and erythema multiforme (EM) major because of overlap in clinical presentations. SJS and EM major associated with Mycoplasma pneumoniae have been reported to occur in children, but Mycoplasma is more commonly reported with SJS. We sought to further characterize Mycoplasma-associated mucocutaneous disease. Through retrospective chart review over 10 years, six children hospitalized with a diagnosis of SJS who also tested positive for Mycoplasma infection were reviewed. Using documented physical examinations and photographs, diagnoses of SJS or EM major were retrospectively made based upon cutaneous lesional morphology employing the classification system proposed by Bastuji-Garin et al. The majority of patients were boys, with limited acral cutaneous lesions. All patients required prolonged hospitalization because of mucosal involvement and had good short-term outcomes. When the classification system was retrospectively applied, five of the six patients were reclassified with a diagnosis of EM major instead of SJS. Children with Mycoplasma-associated EM major and SJS in our small retrospective series appeared to have significant mucosal involvement but more limited cutaneous involvement with lesional morphology, which is more characteristic of EM major.

Secondary bacterial infection and empirical antibiotic use in toxic epidermal necrolysis patients.

The objective of this study was to determine rates of positive bacterial cultures in patients with extensive toxic epidermal necrolysis, the rate of bacteremia, whether empirical antibiotics had been commenced, and their effectiveness when commenced. The authors conducted a retrospective chart review of patients with extensive toxic epidermal necrolysis between January 2001 and December 2012 admitted to the Victorian Adult Burns Service, Melbourne, Australia, with respect to the amount of positive cultures, number and type of organisms identified, whether empirical antibiotics had been commenced, and whether antibiotics were effective against organisms cultured. A total of 27 patients were admitted over the study period of 11 years. Seventeen of these patients developed at least one positive bacterial culture. Patients who grew positive cultures had a longer length of stay in intensive care unit and in hospital overall compared with patients who did not grow positive cultures. Thirty-five positive cultures were collected overall, with empirical antibiotics commenced in 22 cases. In terms of sensitivity, antibiotics were appropriate in 19 cases. Four patients developed bacteremia, two of whom died. This study does not dispute the generally accepted practice of avoiding prophylactic antibiotics in toxic epidermal necrolysis patients, but in the context of a relatively low rate of bacteremia in this patient population, advises appropriate and targeted empirical antibiotic use where clinical infection is suspected.