EM minor EM major SJS SJS-TEN TEN
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1 North American study of pediatric SJS and TEN: Setting diagnostic criteria, systematic review and retrospective cohort analysis comparing outcomes of common treatments Michele Ramien, MDCM, FRCPC Dermatology, DABD Children s Hospital of Eastern Ontario/Alberta Children s Hospital On behalf of a PeDRA collaboration October 26, 2018
2 EM minor EM major SJS SJS-TEN TEN
3 This talk highlights our group s results and future directions Setting diagnostic criteria Systematic review and meta-analysis Retrospective cohort plan
4 Setting diagnostic criteria
5 Supported by: Redefining severe cutaneous reactions in children Amin Bahubeshi, Michele Ramien Children s Hospital of Eastern Ontario; Larry Eichenfeld Rady Children s Hospital; Irene Lara-Corrales, Elena Pope SickKids Hospital; Amy Jo Nopper Children s Mercy Kansas City; Moise Levy - Dell Children's Medical Center of Central Texas; Neil Shear Sunnybrook Health Sciences Centre BACKGROUND The RegiSCAR cohort study revolutionized the management of adult SJS-TEN but the results can t be directly applied to the pediatric population. Reliable and validated data informing the best intervention in the management of pediatric SJS/TEN are lacking. Case definitions are a critical first step to study the SJS/TEN spectrum in children. OBJECTIVE Create and validate pediatric-specific case definitions for the following: SJS, TEN, EM, and infection-related mucositis (including MIRM). METHODS 1. Literature review of key sources. 2. Expert panel assembled. 3. Modified nominal group technique for consensus: Literature review presented to expert panel, organized and informal discussion of diagnostic categories. Proposal of case definition elements and categories. 4. Literature review and case definition elements presented at the inflammatory session at PeDRA. Online survey on most relevant elements. 5. Expert panel reviewed survey results and proposed case definitions. RESULTS: PROPOSED REVISED CLASSIFICATION AND CRITERIA Current classification EM minor EM major SJS SJS-TEN TEN (M)IRM Revised classification Erythema multiforme 1. Patient must have fixed typical or atypical papular targets* 2. Patient must have at least 2 of the following: a) Acral distribution b) Recent history or lab evidence of HSV infection c) Systemically well d) Mucosal involvement Supporting features Recurrent episodes Symmetrical distribution Individual lesions last at least 5 days and resolve without sequelae Skin lesions fully developed within 72 hours What s new? Minor and major are grouped together Emphasis on HSV as a trigger Reactive infectious mucocutaneous or mucosal-predominant eruption (RIME) 1. Patient must have at least 2 of the following: a) Vesiculobullous skin lesions (<10%BSA) without typical papular targets b) Erosive mucositis, with at least 2 mucosal surfaces involved c) Non-contributory medication history** 2. Patient must have evidence of relevant infection as indicated by at least one of the following: a) Clinical symptoms (including cough, fever, malaise, arthralgias) b) Radiologic evidence of pneumonia c) Laboratory evidence of acute infection (ie. PCR, IgM, or similar) Supporting features Prodromal symptoms Histology excluding other immunobullous disease What s new? Encompasses MIRM, MPAM, mucositispredominant eruptions Considers infections other than mycoplasma Epidermal necrolysis 1. Patient must have rapidly progressing erythema and epidermal detachment with a relevant medication history* and histology that excludes alternative diagnoses 2. Patient must have at least 2 of the following: a) At least10% detached or detachable skin surface area b) Severe involvement of 2 or more mucosal surfaces c) Constitutional and site specific symptoms*** Supporting features Tender skin in the absence of other features of SSSS Generalized distribution and centrifugal Flat atypical targets What s new? Includes SJS, SJS-TEN, and TEN Relevant medication essential **Typical papular targets are described as well-defined round <3cm and having three concentric zones: a bright red outer ring, a paler pink and edematous center ring, and a dusky or purpuric-appearing center. An atypical papular target demonstrates only two zones and/or a poorly defined border. **This includes relevant medication and appropriate time interval. ***Constitutional symptoms include fever, malaise and arthralgias; site specific symptoms depend on areas of involvement and include lung (dyspnea, increased respiratory rate), genital (urethral stricture leading to voiding difficulty), ocular (eye pain, vision impairment), renal (proteinuria, microalbuminuria, hematuria), and gastrointestinal (melena, diarrhea) DISCUSSION Our proposed revised classification stratifies related severe cutaneous reactions by etiology, making it practical for management. The morphology of each category is distinguishable and decreases possible confusion between diagnoses. This classification provides a framework to consider mucositis-predominant disease within the spectrum. It also allows for inclusion of mucositis-predominant disease that is not caused by Mycoplasma. All drug-related reactions are considered one entity, facilitating management as these cases can evolve over time. CONCLUSIONS SJS/TEN spectrum diseases may be more effectively diagnosed to guide management with our proposed revised classification. These case definitions are critical for both practice and to study outcomes. REFERENCES Please see attached reference list.
6 Our main reference for defining severe cutaneous reactions in children is not pediatric-specific and may lead to misdiagnosis Clinical Classification of Cases of Toxic Epidermal Necrolysis, Stevens-Johnson Syndrome, and Erythema Multiforme Sylvie Bastuji-Garin, MD; Berthold Rzany, MD; Robert S. Stern, MD; Neil H. Shear, MD, FRCPC; Luigi Naldi, MD; Jean-Claude Roujeau, MD Bastuji-Garin S et al. (1993). Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Archives of Dermatology, 129(1),
7 Reliable diagnosis à Better outcome data à Better treatment/management for patients
8 PART 4: INFLAMMATO annu. tinea dosis). necese diagforme thema ratum us will eristic ere are E may isease. a marthese enous Fig Cutaneous features of toxic epidermal necrolysis (TEN). EM is best regarded as a self limiting cytotoxic dermatitis resultcharacteristic dusky red color of the early macular eruption in TEN. Lesions ing from cell mediated hypersensitivity most commonly to lesions drugs with dermal with this color often progress to full-blown necrolytic or infection. It presents clinically with a spectrum of macular, papepidermal detachment. ular or urticarial lesions, as well as the classic acral iris or target lesions (Figure 47.1). Lesions may involve the palms or trunk, as well as the oral and genital mucosal membranes, which are associated with erosions. On the other hand, SJS, first described in 1922, comprises extensive EM of the trunk and mucous membranes (Figure 47.2), accompanied by fever, malaise, myalgia and arthralgia [6,7]. Lyell first reported TEN in 1956 [8], which was characterized by extensive, sheet like, skin erosions with widespread purpuric macules or flat, atypical, target lesions (Figure 47.3), accompanied by severe involvement of the conjunctival, corneal (Figure 47.4), irideal, buccal, labial and genital mucous membranes [9,10]. Our revised classification improves correlation with cause and management and includes mucositis-predominant disease n syndrome) atingly pt and of one svirus) d TEN 19 and may be Erythema multiforme <10% >30% 10-30% = Surface area of epidermal detachment SJS = Stevens-Johnson syndrome = Detached epidermis TEN = Toxic epidermal necrolysis Reactive infectious Epidermal necrolysis Fig Spectrum of disease based upon surface area of epidermal detachment. mucosal-predominant 466 Pediatric Dermatology Vol. 34 No. 4 July/August 2017 eruption (RIME) A EM minor Figure 47.1 Classic target lesion in erythema multiforme. A Figure 1. Severe cheilitis with multiple erosions and EM hemorrhagic major crusts on the upper and lower lips. Erosions SJS B SJS-TEN TEN were also noticeable on the and on the Fig. oral 20.12mucosa Stevens Johnson syndrome (SJS) versus SJS TEN overlap. A In anterior part of the tongue. addition to mucosal involvement and numerous dusky lesions with flaccid (M)IRM iffiths, Jonathan Barker, Tanya Bleiker, Robert Chalmers and Daniel Creamer. bullae, there are areas of coalescence and multiple sites of epidermal Ltd. B C detachment. Because the latter involved >10% body surface area, the patient including MIRM sine rash classified asmarkers having SJS TEN The remainder of the was biochemical were overlap. B Close-up of epidermal detachment, Fig Clinical features of toxic epidermal necrolysis (TEN). A Detachment whose appearance has been likened to wet cigarette paper. within normal parameters. Figure 2. Targetoid erosion on the glans penis that made of large sheets of necrolytic epidermis (>30% body surface area), leading foreskin retraction painful. With the physical findings and concern for to extensive areas of denuded skin. A few intact bullae are still present. dehydration andoforal discomfort, preliminary diagb Hemorrhagic crusts with mucosal involvement. C Epidermal detachment palmar skin. noses of primary herpes infection andpatients possible predicting which with SJS are likely to progress towards full- atypical pneumonia wereblown considered andcurrently the patient TEN are unavailable. in terms of classification, morphology, and pathogenin TEN, are several that(2 4). have been correlated with poor received supportive therapy with there rehydration andfactorsesis MIRM is more prevalent in boys. In outcome, including increasing and extent of epidermal detachment. pain medication. Intravenous acyclovir 5 mg/kg was agepatients in distinguishing between the two diseases. Differentiation is based with MIRM there is a predominance of In addition, the numbercare, of medications, elevation of serum urea, primarily on clinical characteristics, especially the of the alsoappearance administered. After the first day of inpatient mucosal involvement, with creativariable cutaneous and glucose levels, neutropenia, lymphopenia and thrombocytotarget lesions and their distribution. To retain the diagnosis erosions of EM, onnine he developed the glans penis (Fig. 2). No involvement. Prominent mucositis, particularly oral penia have been statistically to poor outcome. Late withdrawal typical target lesions must exist, whereas SJS should be considered if present. cutaneous lesions were Mucositis secondary linked involvement, is nearly universal in MIRM and is a
9 Poster 15 Current classification EM minor EM major SJS SJS-TEN TEN (M)IRM Revised classification Erythema multiforme 1. Patient must have fixed typical or atypical papular targets* 2. Patient must have at least 2 of the following: a) Acral distribution b) Recent history or lab evidence of HSV infection c) Systemically well d) Mucosal involvement Supporting features Recurrent episodes Symmetrical distribution Individual lesions last at least 5 days and resolve without sequelae Skin lesions fully developed within 72 hours Reactive infectious mucocutaneous or Epidermal necrolysis mucosal-predominant eruption (RIME) 1. Patient must have at least 2 of the following: a) Vesiculobullous skin lesions (<10%BSA) without typical papular targets b) Erosive mucositis, with at least 2 mucosal surfaces involved c) Non-contributory medication history** 2. Patient must have evidence of relevant infection as indicated by at least one of the following: a) Clinical symptoms (including cough, fever, malaise, arthralgias) b) Radiologic evidence of pneumonia c) Laboratory evidence of acute infection (ie. PCR, IgM, or similar) Supporting features Prodromal symptoms Histology excluding other immunobullous disease 1. Patient must have rapidly progressing erythema and epidermal detachment with a relevant medication history* and histology that excludes alternative diagnoses 2. Patient must have at least 2 of the following: a) At least10% detached or detachable skin surface area b) Severe involvement of 2 or more mucosal surfaces c) Constitutional and site specific symptoms*** Supporting features Tender skin in the absence of other features of SSSS Generalized distribution and centrifugal Flat atypical targets What s new? Minor and major are grouped together Emphasis on HSV as a trigger What s new? Encompasses MIRM, MPAM, mucositispredominant eruptions Considers infections other than mycoplasma What s new? Includes SJS, SJS-TEN, and TEN Relevant medication essential **Typical papular targets are described as well-defined round <3cm and having three concentric zones: a bright red outer ring, a paler pink and edematous center ring, and a dusky or purpuric-appearing center. An atypical papular target demonstrates only two zones and/or a poorly defined border. **This includes relevant medication and appropriate time interval. ***Constitutional symptoms include fever, malaise and arthralgias; site specific symptoms depend on areas of involvement and include lung (dyspnea, increased respiratory rate), genital (urethral stricture leading to voiding difficulty), ocular (eye pain, vision impairment), renal (proteinuria, microalbuminuria, hematuria), and gastrointestinal (melena, diarrhea)
10 Systematic review and meta-analysis
11 What is the best treatment for SJS, SJS-TEN,TEN in children? Del Pozzo-Magana et. al (2011) 31 studies 128 cases 4 groups: IVIG Corticosteroids Dressings +/- debridement Supportive care
12 A comprehensive search strategy (inception 2018) identified 257 studies with 1617 patients after screening PRISMA study flow diagram
13 Baseline characteristics were similar amongst diagnostic groups, other than that SJS-TEN was mainly diagnosed in males (84%) Overall 26% 43% 31% Average age / years
14 Antibiotics and anticonvulsants were the most common causes; analgesic/nsaid use was reported in 9% Many others (20%) Sulfonamides (6%) Antibiotics (34%) Analgesics (9%) Anticonvulsants (31%)
15 Data was extracted for the following primary and secondary outcomes: 1ry: SCORTEN Mortality Time to death Time to arrest of blister formation 2ry: Time to re-epithelialization Length of hospital stay Duration of followup
16 Regression models were fitted to estimate relationships between treatment and diagnosis for each of these outcomes 1ry: Mortality Time to arrest of blister formation 2ry: Time to re-epithelialization Length of hospital stay
17 Mortality rates were lower in pediatric patients than in adults and SJS-TEN had the lowest mortality rate Study reported mortality stratified by diagnosis SJS (n=837) SJS-TEN (n = 232) TEN (n=548) 2% 0.5% 11% Overall mortality = 4.9%
18 Mortality effect was assessed for supportive care, corticosteroids, IVIG, and combination IVIG + corticosteroids Treatment Number of patients Supportive care 732 Corticosteroids only 504 IVIG only 186 IVIG + corticosteroids 103 Other 92
19 Treatment with IVIG, corticosteroids, or both vs supportive care did not have a significant effect on mortality Post-model fit contrasts from multivariable regression on mortality Mortality Effect Treatment Group Estimate (95% CI) Odds Ratio (95% CI) P value* IVIG vs. Supportive care (-1.52 to 1.21) 0.86 (0.22 to 3.37) CS vs. Supportive care (-1.71 to 1.08) 0.73 (0.18 to 2.95) IVIG + CS vs. Supportive care (-3.80 to 0.98) 0.24 (0.02 to 2.67) *Level of significance was adjusted for multiple comparisons, a p<0.008 was used to detect statistical significance.
20 Surrogate markers of healing (secondary outcomes) were available for fewer patients Multivariable ordinary least squares regression to model treatment grouping with reported time to re-epithelialization, using supportive care as the reference treatment group Time to Arrest of Blistering Progression (days) Time to Re-Epithelialization (days) Length of Hospital Stay (days) Model coefficient P value* Model coefficient P value* Model coefficient P Treatment group (adjusted 95% CI) (adjusted 95% CI) (adjusted 95% CI) value* Surgical N/A N/A (-9.88 to -0.62) (7.21 to 17.83) <0.001 debridement only IVIG only (-9.13 to -0.20) ( to -7.63) < (-1.09 to 7.06) CS only (-4.35 to -0.29) ( to -3.25) (-8.78 to 2.73) Cyclosporine only (-8.90 to -0.58) ( to -3.88) < (1.78 to -1.78) TNF inhibitors (with any other) ( to -2.31) ( to -4.10) < (1.25 to 18.22) n = 102 n = 67 n = 238 *Level of significance was adjusted for multiple comparisons, a p<0.01 was used to detect statistical significance.
21 TNF-inhibitors decreased time to arrest of blistering progression vs supportive care (in a small sample of patients) Multivariable ordinary least squares regression to model treatment grouping with reported time to re-epithelialization, using supportive care as the reference treatment group Time to Arrest of Blistering Progression (days) Time to Re-Epithelialization (days) Length of Hospital Stay (days) Model coefficient P value* Model coefficient P value* Model coefficient P Treatment group (adjusted 95% CI) (adjusted 95% CI) (adjusted 95% CI) value* Surgical N/A N/A (-9.88 to -0.62) (7.21 to 17.83) <0.001 debridement only IVIG only (-9.13 to -0.20) ( to -7.63) < (-1.09 to 7.06) CS only (-4.35 to -0.29) ( to -3.25) (-8.78 to 2.73) Cyclosporine only (-8.90 to -0.58) ( to -3.88) < (1.78 to -1.78) TNF inhibitors (with any other) ( to -2.31) ( to -4.10) < (1.25 to 18.22) n = 102 n = 67 n = 238 n = 4 *Level of significance was adjusted for multiple comparisons, a p<0.01 was used to detect statistical significance.
22 All treatments except surgical debridement decreased time to reepithelialization vs supportive care Multivariable ordinary least squares regression to model treatment grouping with reported time to re-epithelialization, using supportive care as the reference treatment group Time to Arrest of Blistering Progression (days) Time to Re-Epithelialization (days) Length of Hospital Stay (days) Model coefficient P value* Model coefficient P value* Model coefficient P Treatment group (adjusted 95% CI) (adjusted 95% CI) (adjusted 95% CI) value* Surgical N/A N/A (-9.88 to -0.62) (7.21 to 17.83) <0.001 debridement only IVIG only (-9.13 to -0.20) ( to -7.63) < (-1.09 to 7.06) CS only (-4.35 to -0.29) ( to -3.25) (-8.78 to 2.73) Cyclosporine only (-8.90 to -0.58) ( to -3.88) < (1.78 to -1.78) TNF inhibitors (with any other) ( to -2.31) ( to -4.10) < (1.25 to 18.22) n = 36 n = 11 n = 8 n = 4 n = 102 n = 67 n = 238 *Level of significance was adjusted for multiple comparisons, a p<0.01 was used to detect statistical significance.
23 Surgical debridement significantly increased length of hospital stay vs supportive care; no other treatment had an impact Multivariable ordinary least squares regression to model treatment grouping with reported time to re-epithelialization, using supportive care as the reference treatment group Time to Arrest of Blistering Progression (days) Time to Re-Epithelialization (days) Length of Hospital Stay (days) Model coefficient P value* Model coefficient P value* Model coefficient P Treatment group (adjusted 95% CI) (adjusted 95% CI) (adjusted 95% CI) value* Surgical N/A N/A (-9.88 to -0.62) (7.21 to 17.83) <0.001 debridement only IVIG only (-9.13 to -0.20) ( to -7.63) < (-1.09 to 7.06) CS only (-4.35 to -0.29) ( to -3.25) (-8.78 to 2.73) Cyclosporine only (-8.90 to -0.58) ( to -3.88) < (1.78 to -1.78) TNF inhibitors (with any other) ( to -2.31) ( to -4.10) < (1.25 to 18.22) n = 102 n = 67 n = 238 n = 7 n = 2 *Level of significance was adjusted for multiple comparisons, a p<0.01 was used to detect statistical significance.
24 To summarize our systematic review and meta-analysis findings: Low mortality rate Treatment did not significantly reduce mortality Some treatments may reduce healing time
25 Strengths Summarizes available data Large number of patients Weaknesses Missing data Included studies low quality evidence Food for thought: Would outcomes be different with our revised classification? How does timing of treatment affect response? What is the best primary outcome?
26 Retrospective cohort study
27 47.1 CHAPTER 47 Reactive Inflammatory Erythemas SECTION Malcolm Rustin1 and Rino Cerio2 4 1 Royal SPECTRUM OF DISEASE BASED UPON SURFACE AREA OF EPIDERMAL DETACHMENT URTICARIAS, ERYTHEMAS AND PURPURAS Free London NHS Foundation Trust, London, UK 2 The Royal London Hospital, Bart s Health NHS Trust, London; and Queen Mary s Medical and Dental School, University of London, London, UK SJS-TEN overlap SJS TEN The aim of this multicenter retrospective cohort study is identify best management for severe cutaneous reactions in children Erythema annulare centrifugum, 47.8 Erythema multiforme, 47.1 Erythema gyratum repens, Annular erythema of infancy, 47.6 Erythema marginatum, Introduction Multiple skin conditions can present with ring like or annular lesions for which a specific diagnosis can be made (e.g. tinea corporis, granuloma annulare, psoriasis or annular sarcoidosis). This chapter describes a group of conditions that do not necessarily lead to a specific underlying diagnosis and may pose diagnostic and therapeutic problems. It includes erythema multiforme (EM), annular erythema of infancy, necrolytic migratory erythema (NME), erythema annulare centrifugum, erythema gyratum repens and erythema marginatum. Subacute cutaneous lupus will be covered in Chapter 54. Each eruption may have characteristic features and although diagnosis of EM is often easy and there are a limited number of underlying causes, the diagnosis of NME may take time in view of the different manifestations of the disease. Physicians should be alert to the subtle eruption of erythema marginatum and the importance of diagnosing rheumatic fever. These cutaneous signs therefore present a challenge with heterogenous diseases presenting with varying morphologies. Eryth hema multtiform me Comprehensive Definition and terminology Data Collection Form Until recently, erythema multiforme (EM), Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN or Lyell syndrome) were considered to form a spectrum from mild to fulminatingly severe cases. There has been a re evaluation of this concept and a tendency to consider EM minor and EM major as part of one spectrum, often following infections (especially with herpesvirus) and sometimes due to drug reactions. On this basis SJS and TEN are separable from EM. The topic is discussed in Chapter 119 and is more closely linked to drug sensitivities. SJS and TEN may be regarded as severe variants of a single disease [1 5]. Necrolytic migratory erythema, Key references, EM is best regarded as a self limiting cytotoxic dermatitis resulting from cell mediated hypersensitivity most commonly to drugs or infection. It presents clinically with a spectrum of macular, papular or urticarial lesions, as well as the classic acral iris or target lesions (Figure 47.1). Lesions may involve the palms or trunk, as Fig Cutaneous features of toxic epidermal necrolysis (TEN). well as the dusky oral and genital membranes, which Characteristic red color of the mucosal early macular eruption in TEN. Lesionsare associwith colorerosions. often progress full-blown lesions with dermal in 1922, atedthis with Ontothe other necrolytic hand, SJS, first described epidermal detachment. comprises extensive EM of the trunk and mucous membranes (Figure 47.2), accompanied by fever, malaise, myalgia and arthralgia [6,7]. Lyell first reported TEN in 1956 [8], which was characterized by extensive, sheet like, skin erosions with widespread purpuric macules or flat, atypical, target lesions (Figure 47.3), accompanied by severe involvement of the conjunctival, corneal (Figure 47.4), irideal, buccal, labial and genital mucous membranes [9,10]. Erythema multiforme PART 4: INFLAMMATORY Introduction, 47.1 <10% >30% 10-30% = Surface area of epidermal detachment SJS = Stevens-Johnson syndrome = Detached epidermis TEN = Toxic epidermal necrolysis Reactive infectious Epidermal necrolysis Fig Spectrum of disease based upon surface area of epidermal mucosal-predominant detachment. 466 Pediatric Dermatology Vol. 34 No. 4 July/August 2017 eruption (RIME) A Figure 1. Severe cheilitis with multiple erosions and hemorrhagic crusts on the upper and lower lips. Erosions were also noticeable on the oral mucosa and on the anterior part of the tongue. A B The remainderfig. of the biochemical markers syndrome were Stevens Johnson (SJS) versus SJS TEN overlap. A In within normal addition parameters. to mucosal involvement and numerous lesions with flaccid Figure 2. dusky Targetoid erosion on the glans penis that made foreskin retraction With the physical findings and of concern for and bullae, there are areas coalescence multiple sitespainful. of epidermal B C dehydration and oral discomfort, preliminary diagdetachment. Because the latter involved >10% body surface area, the patient noses of primary herpes infection possible was classified as havingand SJS TEN overlap. B Close-up of epidermal detachment, Figure 47.1Clinical Classicfeatures target lesion in epidermal erythema multiforme. atypical pneumonia consideredhas andbeen the patient Fig of toxic necrolysis (TEN). A Detachment in terms of classification, whosewere appearance likened to wet cigarette paper. morphology, and pathogenreceived supportive therapy with rehydration and esis (2 4). MIRM is more prevalent in boys. In of large sheets of necrolytic epidermis (>30% body surface area), leading patients with MIRM there is a predominance of to extensive areas of denuded skin. A few intact bullae are still present. pain medication. Intravenous acyclovir 5 mg/kg was Rook s Textbook of Dermatology, Ninth Edition. Edited by Christopher Griffiths, Jonathan Barker, Tanya Bleiker, Robert Chalmers and Daniel Creamer. also administered. After the first day of inpatient care, mucosal involvement, with variable cutaneous B Hemorrhagic crusts with mucosal involvement. C Epidermal detachment of he developed erosions on thewhich glans penis (Fig. 2). No SJS involvement. Prominent oral 2016 John Wiley & Sons, Ltd. Published 2016 by John Wiley & Sons, Ltd. palmar skin. predicting patients with are likely to progressmucositis, towardsparticularly fullcutaneous lesions were present. Mucositis secondary involvement, is nearly universal in MIRM and is a Companion website: blown TEN are currently unavailable. to mycoplasma infection was suspected, and the major cause of morbidity and hospitalization (1). In TEN, there are several factors that havemirm been has correlated with poor (1). patient began therapy with azithromycin and methylhowever, an excellent prognosis outcome, including increasing extent of epidermal detachment. prednisolone. A polymerase chain reaction (PCR)age andthe in distinguishing between the two diseases. Differentiation is based pathophysiology underlying MIRM is thought for herpes virus infection tested negative. In addition, the number of medications, elevation of serum creati-and antito involve polyclonal B-cell urea, proliferation primarily on clinical characteristics, especially the appearancesample of the for Mycoplasma pneumonia bodylymphopenia production after pneumoniae infection, nine and glucose levels, showed neutropenia, and M. thrombocytotarget lesions and their distribution. To retain the diagnosisserologic of EM,testing positive immunoglobulin G (IgG) of 21.1 and mayoutcome. result in Late skin damage from immune penia have been titers statistically linkedwhich to poor withdrawal typical target lesions must exist, whereas SJS should be considered if low IgM (2.6), suggesting a previous infection. PCR 328 complex deposition and complement activation (5). of the causative drug is also associated with a less favorable outcome. target lesions are atypical (see Table 20.1). Unfortunately, criteria testing for on an oropharyngeal swab sample was negathis mechanism differs from the type IV delayed-type tive for M. pneumonia, but positive for Chlamydia hypersensitivity reaction involved in EM, SJS, and pneumoniae. Symptomatic resolution was achieved TEN (6). Molecular mimicry between mycoplasma P1 after 5 days of treatment and no further complicaadhesion molecules and a keratinocyte antigen has tions were observed. also been hypothesized, as well as a possible genetic susceptibility (7,8). In the current study we present a case of mucositis DISCUSSION without rash in the context of C. pneumoniae respiin a recent review by Canavan et al (1) based on 202 ratory infection. C. pneumoniae infection is often published cases, the term M. pneumonia induced rash asymptomatic (60% 80% of all infections) (9). Most and mucositis (MIRM) was proposed as a clinical infections involve the upper and lower respiratory term to include the different mucocutaneous eruptions tracts. In some cases, infection transforms into a associated with mycoplasma infection, distinguishing chronic, clinically oligosymptomatic or asympthis syndrome from drug-induced Stevens Johnson tomatic form that has been linked to coronary artery syndrome (SJS), toxic epidermolytic necrosis (TEN), disease, endocarditis, atherosclerosis, hypertension, and herpes-related erythema multiforme (EM), which vasculitis, multiple sclerosis, sarcoidosis, and asthma. are diseases that have historically defied concurrence Chronic forms of infection related to C. pneumoniae EM minor EM major SJS (M)IRM including MIRM sine rash SJS-TEN TEN
28 Reliable diagnosis/classification à Better outcome data à Better treatment/management for patients
29
30 PeDRA gives me a platform for collaborating with investigators on pediatric dermatology research. 40+ research studies, 215 members, 130 institutions
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