Cutaneous manifestations of hiv infectiontashagarwal
Dermatological problems occur in more than 90% of patients with human immunodeficiency virus (HIV) infection. In some patients, skin is the first organ affected. Skin diseases have proved to be sensitive and useful measures by which HIV progression can be monitored.
Erythroderma is defined as the scaling erythematous dermatitis involving 90% or more of the cutaneous surface.
Also known as exfoliative dermatitis
Idiopathic exfoliative dermatitis – also known as the “red man syndrome”, is characterized by marked palmoplantar keratoderma, dermatopathic lymphadenopathy,increased IgE.
Increased skin perfusion leads to
Temperature dysregulation >
Resulting in skin loss and hypothermia >
High output state >
Cardiac failure
BMR raises to compensate for heat loss
Increased dehydration due to transpiration (similar to burns)
All lead to negative nitrogen balance and characterized by edema, hypoalbuminemia, loss of muscle mass.
Drug reaction with eosinophilia and systemic symptoms & acute generalized exanthematous pustulosis 2019
Presented by Nattasasi Suchamalawong, MD.
November 15, 2019
Cutaneous manifestations of hiv infectiontashagarwal
Dermatological problems occur in more than 90% of patients with human immunodeficiency virus (HIV) infection. In some patients, skin is the first organ affected. Skin diseases have proved to be sensitive and useful measures by which HIV progression can be monitored.
Erythroderma is defined as the scaling erythematous dermatitis involving 90% or more of the cutaneous surface.
Also known as exfoliative dermatitis
Idiopathic exfoliative dermatitis – also known as the “red man syndrome”, is characterized by marked palmoplantar keratoderma, dermatopathic lymphadenopathy,increased IgE.
Increased skin perfusion leads to
Temperature dysregulation >
Resulting in skin loss and hypothermia >
High output state >
Cardiac failure
BMR raises to compensate for heat loss
Increased dehydration due to transpiration (similar to burns)
All lead to negative nitrogen balance and characterized by edema, hypoalbuminemia, loss of muscle mass.
Drug reaction with eosinophilia and systemic symptoms & acute generalized exanthematous pustulosis 2019
Presented by Nattasasi Suchamalawong, MD.
November 15, 2019
Introduction: malignant syphilis is an uncommon form of secondary syphilis.This presentation usually occurs in immunocompromised patients, especially in those ones infected by human immunodeficiency virus (HIV). However, it is known that it might exceptionally affect individuals with normal immune response.
Introduction: malignant syphilis is an uncommon form of secondary syphilis.This presentation usually occurs in immunocompromised patients, especially in those ones infected by human immunodeficiency virus (HIV). However, it is known that it might exceptionally affect individuals with normal immune response.
Case report: in this manuscript, we report a case with ocular involvement in a male immunocompetent patient. He had extended skin lesions and conjunctival hyperemia on the right eye. After the laboratorial investigation we confirmed syphilis and excluded human immunodeficiency virus (HIV) infection. Considering he had uveitis, the case was conducted as neurosyphilis.and the treatment was made with Ceftriaxone, followed by excellent clinical response.
Conclusion: given the increasing number of cases of syphilis, in patients with polymorphic skin lesions associated with systemic
symptoms, it is important to exclude immunosuppression and even in immunocompetent.subjects this condition should always be a differential diagnosis.
Keywords: Malignant Syphilis; Immunocompetent; Uveitis
Demographic studies of a disease can reveal the characteristics of that disease among a specific population and will help the physicians to achieve a more accurate perception about it.The demographic of Lichen PlanoPilaris (LPP) among the Iranian population is unknown. The aim of this study is to describe the clinical, demographic, and histopathologic findings of lichen planopilaris in the Iranian population.
A NOVEL STUDY OF LICHEN PLANOPILARIS AMONG DIFFERENT IRANIAN ETHNICITIES BASE...ijcsit
Introduction: Demographic studies of a disease can reveal the characteristics of that disease among a specific population and will help the physicians to achieve a more accurate perception about it.The demographic of Lichen PlanoPilaris (LPP) among the Iranian population is unknown. The aim of this study is to describe the clinical, demographic, and histopathologic findings of lichen planopilaris in the Iranian population.
Materials and Methods: In this cross-sectional study, all the patients with Lichen planopilaris were referred to the dermatology clinic of Imam Khomeini hospital from 2013 to 2015. Lichen planopilaris can be diagnosed by collecting histological evidence, dermatological examination, and clinical diagnosis. Their demographic characteristics, drug histories, onset of disease, and family histories were obtained by written questionnaire. Additionally, this study employed SPSS v.20 as the statistical analysis software.
Results: One hundred patients were enrolled in this study. With an average age of 47.11 years, 78% of the patients were female, and 50 of these were housewives. The patients included were often from Tehran with Fars ethnicity. Among these patients, 7 had alopecia areata skin disease, and 10 of them suffered from thyroid disease. Most of the histopathology samples collected from these biopsies revealed degeneration of the basal layer of the follicular structure, perifollicular fibrosis, inflammatory cells, and atrophy of the pilosebaceous structures.
Conclusion: Both the age spectrum and the disease distribution of LPP among the Iranian population were very diverse when compared to previous studies. Moreover, this study helps the physicians to have a brighter vision about the main reason and cause of LPP spread among diverse Iranian Ethnicities.
Upsurge of Cases of Lichen Planus in Iraqi Population in Baghdad City with Fr...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
A Comparative Study of the Efficacy of 5 Days and 14 Days Ceftriaxone Therapy...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Immunology Pathway of During Autoimmune Disease: A Review Articlekomalicarol
Dermatitis herpetiformis or also known as
duhring disease is a rare autoimmune vesicobulosa disease, specific and recurrent chronic in nature and has a relationship with celiac
disease and gluten-sensitive enteropathy. The diagnosis of dermatitis herpetiformis is based on a combination of physical examination, routine histopathological examination, immunofluorescence
examination, and serological testing. The typical histopathological appearance of dermatitis herpetiformis when examined using
a light microscope is a subepidermal cleft with neutrophils and
several eosinophils in the papillary dermis. immunofluorescence
examination is an examination that is also important for definitive
diagnosis.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
2. Outline
• Epidemiology and Risk Factors
• Diagnosis, Differential Diagnosis and Severity Assessment
• Pathophysiology
• Investigations and Causative Drugs
• Complications
• Management
3. Introduction
• In 1922, 2 US Physicians, Stevens and Johnson, described acute mucocutaneous
syndrome in 2 young boys with severe purulent conjunctivitis, severe stomatitis
with extensive mucosal necrosis and “EM-like” cutaneous lesions, became
“Stevens-Johnson Syndrome”
• In 1956, Alan Lyell described 4 patients with an eruption “resembling scalding of
the skin objectively and subjectively”, he called “Toxic epidermal necrolysis”
• SJS/TEN: delayed-type hypersensitivity reaction to drugs type IV-c (cytotoxicity of
drug-specific T cells)
Wolfram H. et al. Bolognia 4th Edition 2018.
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
4. Epidemiology
• USA-based, 2009 to 2012 - Incidence per million of 8.61 to 9.69 for SJS, 1.46 to 1.84 for
SJS/TEN, and 1.58 to 2.26 for TEN
• Associated with hematological malignancies and certain infections (HIV, fungal infections)
as well as liver and kidney disease
• Mortality rate of SJS 4.8%, SJS/TEN 19.4%, and TEN was 14.8%
• Predictors of mortality - age, pre-existing comorbidities, hematological malignancy,
septicemia, pneumonia, tuberculosis, and renal failure
• Pediatric population (USA) - SJS incidence of 5.3, SJS/TEN of 0.8, and TEN of 0.4 cases per
million
• Mortality rates in children with TEN lower than adults ranging from 0 - 7.5% (overall
mortality in adults approximately 30%)
• Risk factors for mortality - malignancy, septicemia, bacterial infection, and epilepsy
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
5. Epidemiology
• Systematic review of SJS and/or TEN in Thai population from 1995 – 2014
• Reported 540 cases of SJS and/or TEN: 326 (60.4%) – adults, 214 cases (39.6%) – children
• Drug - most common cause in both adults (100%) and children (97.2%)
• Culprit drugs in adults: cotrimoxazole (22%), nevirapine (8.6%) and allopurinol (8.3%), in
children: penicillin (21.1%), phenobarbital (16.3%) and carbamazepine (13.5%)
• Second most common cause in children (2.8%) - Mycoplasma infection
• Most common complication in adult: hepatitis (12%), in children: skin infection (8.4%)
• Death rate in adults: 11.3% VS 6.1% in children (p = 0.04)
• Intravenous corticosteroids treatment in SJS and/or TEN among children was significant
higher than adults (59.2% vs. 27.0%, p<0.01)
Roongpisuthipong W. et al. J Med Assoc Thai 2018; 101 (8):87.
6. Peter et al. J Allergy Clin Immunol Pract 2017; 5:547–563.
7. Risk Factors
• Age group: Children 1–10 years and patients > 80 years
• Autoimmune/collagen vascular disease, lupus erythematosus associated with SJS/TEN
with odds ratio of 16.0 (developed SJS/TEN within first 3 months of drug intake)
• Active cancer (odds ratio 2.01)
• Non-active cancer, depended on underlying malignancy:
Bone and ovarian cancer (odds ratio 9.66)
Hematologic malignancy (odds ratio 9.46)
Cancer of nervous system (odds ratio 2.86)
Cancer of respiratory tract (odds ratio 2.67)
• Acute kidney disease (odds ratio 6.00)
• Patients using allopurinol - risk highest within first 84 days (odds ratio 20.48)
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
8. Risk Factors
• Independent risk factor for SJS/TEN = HIV infection (increased a 100-fold)
• Sulfamethoxazole/trimethoprim (SMX/ TMP) - most frequent drug inducing TEN
in HIV-patients
• Highest risk in patients with HIV/tuberculosis co-infection (odds ratio 8.5)
• Maternofetal outcome in SJS/TEN cases - attributed to nevirapine during
pregnancy
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
10. Clinical Features
• Prodrome: fever, stinging eyes, and pain upon swallowing, precede cutaneous
manifestations by 1 - 3 days
• Skin lesions appear first on trunk, spreading to neck, face, and proximal upper
extremities, distal portions of arms and legs are relatively spared, but palms and
soles can be an early site of involvement
• Erythema and erosions of buccal, ocular, and genital mucosae present in >90% of
patients
• Epithelium of respiratory tract involved in 25% of patients with TEN
• GI lesions (e.g. esophagitis, diarrhea) can also occur
• Systemic manifestations: fever, lymphadenopathy, hepatitis, cytopenias, and
cholestasis due to vanishing bile duct syndrome
Wolfram H. et al. Bolognia 4th Edition 2018.
11. Clinical Features
Morphology of the skin lesions:
• First, erythematous, dusky red, or purpuric macules of irregular size and shape, and
have tendency to coalesce and presence of mucosal involvement and tenderness
• Nikolsky sign = exerting tangential mechanical pressure with finger on
erythematous zones positive if dermal–epidermal cleavage is induced
• Macular lesions can have dusky center, target-like appearance BUT lack three
concentric rings and NOT papular as atypical target lesions of EM
Wolfram H. et al. Bolognia 4th Edition 2018.
12. Clinical Features
• As epidermal involvement progresses toward full-thickness necrosis, the dusky red
macular lesions gray hue (in hours to several days)
• Necrotic epidermis detaches from dermis, and fluid fills space between dermis and
epidermis bulla formation
• Asboe-Hansen sign - Blisters can be extended sideways by slight pressure of the
thumb as more necrotic epidermis is displaced laterally
• Skin resembles wet cigarette paper as it is pulled away by minimal trauma, often
revealing large areas of raw and bleeding dermis - “scalding”
• Extent of necrolysis (using rules as to evaluate the surface area of thermal burns) -
- major prognostic factor
Wolfram H. et al. Bolognia 4th Edition 2018.
15. Diagnosis
• Based on clinical assessment & histopathological findings of subepidermal blisters
with widespread necrosis and apoptotic keratinocytes associated with minimal
lymphocytic inflammatory infiltrate
• 3 forms of epidermal necrolysis: widespread blister formation on erythematous
skin, and flat, atypical target lesions
• Involved body surface area - only undetached and non-detachable erythematous or
violet zones are not included
• Systemic involvement is difficult to distinguish from secondary complications due
to SJS/TEN
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
17. Peter et al. J Allergy Clin Immunol Pract 2017; 5:547–563.
18. Peter et al.
J Allergy Clin Immunol Pract
2017; 5:547–563.
19. Peter et al. J Allergy Clin Immunol Pract 2017; 5:547–563.
20. Peter et al. J Allergy Clin Immunol Pract 2017; 5:547–563.
21. Differential Diagnosis
• Erythema multiforme
• Autoimmune bullous diseases e.g. Linear IgA dermatosis, Epidermolysis bullosa
acquisita
• Autoimmune diseases e.g. bullous lupus erythematosus
• Staphylococcal scalded skin syndrome (SSSS)
• Generalized fixed bullous drug eruption
• Acute generalized exanthematous pustulosis (AGEP)
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
22. Diagnostic Approach
• Confirmed by histopathology: complete epidermal necrosis with subepidermal
blisters and apoptotic keratinocytes associated with minimal lymphocytic
inflammatory infiltrate
• Direct immunofluorescence - NO immunoglobulin deposition
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
24. Wolfram H. et al. Bolognia 4th Edition 2018.
Histopathology
25. Diagnostic Approach
• Identify most likely culprit drug***
• ALDEN: algorithm for assessment of drug causality in epidermal necrolysis
• “ALDEN score should be used as reference method in SJS/TEN”
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
26. Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
ALDEN Score
<0 Very unlikely
0–1 Unlikely
2–3 Possible
4–5 Probable
≥6 Very probable
27. Severity Assessment
• Major prognostic factor = Total body surface area involvement (total mortality of
5% in SJS and 30% in TEN patients)
• Severity-of-illness score for toxic epidermal necrolysis (SCORTEN) based on 7
independent risk factors for epidermal necrolysis
• Good accuracy of SCORTEN in predicting mortality
• Serial determination of SCORTEN within first 5 days was shown to increase its
accuracy in predicting mortality
• Pediatric SCORTEN in children without (A) or with (B) hematopoietic stem cell
transplantation BUT the standard adult SCORTEN was a good predictor for
morbidity in the pediatric population
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
28. Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
33. Pathophysiology
• Cytolytic protein granulysin, produced by CD8+ T cells, NK cells and NKT cells -
primary mediator of keratinocyte cell death in SJS/TEN
• Granulysin found high concentration in serum and blister fluid from patients with
SJS/TEN and plasma levels correlate with disease severity and prognosis
• Granulysin - highest 2–4 days before widespread skin detachment and oral
involvement and elevated up to 2 days after initial skin detachment and mucosal
erosions then levels dropped sharply
• Systemic IL-15, cytokine that activates NK cells and cytotoxic T cells, also correlated
with SJS/TEN severity
• Both IL-15 and granulysin may be used as prognostic markers during acute
SJS/TEN
White et al. J Allergy Clin Immonol Pract 2018;6(1):38-69.
34. Pathophysiology
• Regulatory T cells (Tregs) suppressor function - mediated via a variety of
mechanisms including IL-10 secretion, surface expression of the inhibitory receptor
CTLA-4, and through IL-2 consumption by the high affinity IL-2 receptor CD25
• Treg cells – role in maintaining immune homeostasis in the skin
1) Tregs are less abundant in skin from patients with SJS/TEN compared to erythema
multiforme
2) Circulating Tregs obtained from patients with SJS/TEN display impaired suppressor
function
3) Tregs can prevent epidermal injury in animal TEN model systems
4) Treg-mediated suppression decreases cytotoxic T-cell responses to drug in in vitro
systems
White et al. J Allergy Clin Immonol Pract 2018;6(1):38-69.
35. Pathophysiology
• Increased levels of FasL with a peak 2-4 days before clinical development of skin
detachment and mucosal erosions, then returned to normal within 5 days after
onset of skin/mucosal manifestations
• Elevated serum FasL could be used to differentiate drug allergy and viral exanthem
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
37. Pathophysiology
• sTRAIL, interferon (IFN)-γ, and TNF-α serum concentrations - stably elevated for
longer time during disease course
• TARC (serum thymus and activation regulated chemokine), Th2 chemokine, is not
only found to be significantly elevated in SJS/TEN and other drug allergy reactions
• Not only Th1 but also Th2 cells might be implicated in SJS/TEN
• Elevated serum microRNA-124 levels detected by real-time PCR - showed good
correlation with SCORTEN and extent of skin involvement
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
39. Drug Testing
• Due to severity of the disease, intradermal tests and systemic re-exposure must
be strictly avoided in SJS/TEN
• Patch testing may be considered the only in vivo test
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
40. Drug Testing – Patch Test
• Patch tests sensitivity, yielding positive results in 50 - 58% of patients with AGEP,
50% of patients with maculopapular exanthem, 61 - 64% of patients with DRESS
• BUT disappointing sensitivity of patch-testing in SJS/TEN (0 – 24%), no relevant
adverse side effect
• Only for carbamazepine - sensitivity of patch testing seemed better
• Caution in HIV patients treated with anti-tuberculous medications
• Lehloenya et al. reported 2 systemic reactions during patch testing
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
41. Lymphocyte Transformation Test
• Stimulation of T-cell with a drug, classically by measuring incorporation of
radioactive thymidine into DNA of proliferating cells
• LTT sensitivity > 50% in generalized maculopapular and bullous exanthem, AGEP,
DRESS, and generalized most severe forms of anaphylaxis, validity in TEN is low (<
10%)
• Importance of the right timing of LTT in early phase of SJS/TEN
• Serial LTTs performed 10.5 months apart, showing reduction of proliferation over
time
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
42. Lymphocyte Transformation Test
• To improve sensitivity of LTT, modified assay T regs/CD25 high cells were removed
before incubation increase specificity from 25 - 82% and significant increase of
drug-specific lymphocyte proliferation
• BUT in lamotrigine-induced SJS/TEN did not show significant increase of sensitivity
or proliferation rate
• Alternative and faster approach of measuring T-cell proliferation = analysis of CD69
upregulation by FACS (results available within 48 h compared to 7 days with LTT)
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
43. Other In Vitro Tests
• Conventional IFN-γ ELISPOT
• Evaluation of anti-PD-L1 (programmeddeath-ligand1) antibody, check point
inhibitor, in IFN-γ ELISPOT assay
• Measured granzyme B and IFN-γ release by ELISPOT, as well as upregulation of
granulysin on peripheral blood lymphocytes by FACS
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
44. Drugs Implicated in SJS/TEN
• Median intake time of drugs before symptoms occur = 4 weeks (to 8 weeks after
start drug intake)
• For low-risk drugs or drugs not typically implicated in SJS/TEN - latency to 30
weeks
• High risk drugs: cotrimoxazole as well as other antibiotic sulfonamides, allopurinol,
carbamazepine, phenytoin, phenobarbital, and oxicam-NSAID
• Among newer drugs, nevirapine, lamotrigine, sertraline, and possibly pantoprazole
- frequent inducers of SJS/TEN
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
45. Drugs Implicated in SJS/TEN
Peter et al. J Allergy Clin Immunol Pract 2017; 5:547–563.
46. Drugs Implicated in SJS/TEN
• Allopurinol - most frequent inducer of SJS/TEN in European countries, Israel,
Canada
• Allopurinol has clear dose dependent increase risk in patients taking > 200 mg/day
• In Kenya, SMX/TMP followed by nevirapine - two leading drugs inducing SJS/TEN
• India - antimicrobial drugs > anti-epileptic drugs > NSAIDs
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
47. Drugs Implicated in SJS/TEN
• Among anti-epileptic medications - aromatic anti-convulsives carbamazepine and
phenytoin - leading cause for antiepileptic associated SJS/TEN
• RegiSCAR and EuroSCAR - no link of herpes infection with SJS/TEN. However,
multiple drug use before onset of SJS/TEN could be identified as a relevant risk
factor.
• Most frequent drugs inducing SJS/ TEN in children = anti-infective sulfonamides,
phenobarbital, carbamazepine, and lamotrigine
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
48. Drugs Implicated in SJS/TEN
• Herbal remedies
• Checkpoint inhibitors including CTLA-4 antagonists - causative drugs in patients
with TEN by decreased apoptosis in activated T cells and antagonizing of inhibitory
signals resulting in a higher anti-tumor activity
• Nivolumab (programmed cell death receptor 1; PD-1 antibody) alone or in
combination with ipilimumab may induce TEN or TEN-like reactions with severe
satellite cell necrosis
• Cetuximab, chimeric epidermal growth factor receptor antagonist used in
head/neck and colon cancer
• Small molecules BRAF-V600E inhibitor vemurafenib in metastatic melanoma
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
50. White et al. J Allergy Clin Immonol Pract 2018;6(1):38-69.
51. White et al. J Allergy Clin Immonol Pract 2018;6(1):38-69.
52. Pharmacogenomic Screening
• Benefits and challenges of implementing genetic screening to reduce incidence of
SJS/TEN (from drug regulatory authority in Singapore)
• 2 genetics associations with drug-induced SJS/TEN are relevant
HLA-B*15:02 with carbamazepine
• Allele frequency 14.9%, PPV 6%, NPV nearly 100% (Southeast Asian populations)
HLA-B*58:01 with allopurinol
• Allele frequency 18.5%, PPV 2%, NPV nearly 100%
• Not required as standard of care but could be considered for patients with pre-
existing risk factors such as renal impairment
White et al. J Allergy Clin Immonol Pract 2018;6(1):38-69.
54. Mortality
• RegiSCAR study, fatality rate of SJS/TEN = 23% at 6 weeks with a strict correlation
to severity of the disease and 34% at one year with direct correlation to
comorbidities
• Surviving patients had high prevalence of ocular, skin, and renal sequelae
• SCORTEN of 3 – 6 and delayed referral to burn units > 5 days - predictors of late
fatality
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
55. Complications - Infection
• Acute SJS/TEN, septicemia - leading cause of morbidity and fatality
• Bacterial infection rate = 91.7% and septicemia rate = 62.5%
• Most common pathogens isolated: MRSA and Pseudomonas aeruginosa, and
Candida, Stenotrophomonas and Acinetobacter
• “In antibiotic-associated SJS/TEN secondary resistance of the bacteria was
responsible for the fatal outcome”
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
56. Complications – Respiratory Tract
• Pneumonia - major complication of SJS/TEN with almost half of the patients
requiring mechanical ventilation
• Cultures from bronchial secretions revealed MRSA in 33.3%, Candida albicans in
11.1%, and Gram-negative bacteria in 55.6%
• TEN-associated respiratory symptoms with hypoxemia but normal chest X-ray were
seen
• Complete ENT workup - to diagnose severity of nasopharyngeal mucosal
involvement and evaluate possible pulmonary involvement
• Within 1 year after SJS/TEN, almost all patients showed complete healing of the
oropharyngeal mucosa
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
57. Complications – GI Tract
• Dysphagia - esophageal implication
• Acute: Diffuse and necrotic esophageal manifestations
• Chronic: secondary esophageal strictures
• Small bowel/colon involvement, perforated diverticulitis
• Hepatitis, cholestatic liver disease association with drug-induced SJS/TEN,
secondary acute vanishing bile duct syndrome (VBDS)
• Gastrointestinal symptoms (12.5%), encephalopathy (2.3%), myocarditis (5.7%),
and disseminated intravascular coagulation (8%) - less frequent
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
58. Complications – GU Tract
• Vulvo-vaginal involvement
• Acute: erosions and ulcerations
• Chronic: strictures
• Renal dysfunction, hematuria
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
59. Complications - Ocular
• Acute ocular complications - 40% in SJS and 75% in TEN
• Fifteen months after acute SJS/TEN, late symptoms with dry eye syndrome
• Inflammation and ulceration of the tarsal conjunctiva and lid margin in acute
SJS/TEN with corneal complications
• Early amniotic membrane transplantation - current treatment strategy with the
goal of diminishing risk of secondary scarring and visual impairment
• Cataract - chronic complication of SJS/TEN
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
60. Complications - Ocular
• Systemic therapy neither with IVIG or corticosteroids nor with a combined IVIG and
corticosteroid treatment had significant effect on final visual outcome and the
chronic ocular surface complication score 6 months after SJS
• Topical humanized anti-VEGF monoclonal antibody bevacizumab - decrease in
ocular neovascularization and improvement of visual acuity
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
61. Complications – Long Term
• Long-term skin and eye sequelae
• Chronic eczema, hypo- and hyperpigmentation, nail complications such as
anonychia, dystrophic nails, and pterygium
• Hypertrophic scars and keloids rarely seen following SJS/TEN
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
62. Wolfram H. et al. Bolognia 4th Edition 2018.
Complications
64. Management
• First step, immediate withdrawal of potentially causative drugs, reduce fatality in
SJS/TEN
• Drugs with long half-life higher mortality rate
• Referral to specialized unit, burn centers, for optimized supportive care
• Silver-releasing wraps/dressings - therapy of choice
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
65. Management
• Air-fluidized beds - faster re-epithelialization, lower rate of complications and less
cutaneous infections
• Prefer enteral to parenteral nutrition (parenteral increase fatality rate)
• Although potential effect of empiric antibiotic therapy in the initial stages of
SJS/TEN “ Not generally recommend antibiotic coverage”
• Appropriate information and emotional support
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
66. Management - Corticosteroids
• Concerns of high rate of bacterial infection/sepsis and low rate of re-
epithelialization
• Early dexamethasone pulse therapy in SJS/TEN did not alter the time of disease
stabilization and of re-epithelialization and no increase in sepsis incidence
• EuroSCAR study: glucocorticoids were not found to be superior to supportive care
only in terms of mortality
• Meta-analysis showed comparable results between patients on corticosteroids and
patients receiving supportive care only in general, no increased mortality
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
67. Management - Corticosteroids
• Significant reduction in ocular complications was seen, if steroid pulse therapy was
initiated early
• “Conclusion: early introduction of systemic corticosteroids was life-saving and
should be considered as a low-cost therapy in countries with a limited health
budget”
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
68. Management - IVIG
• IVIG - inhibition of Fas-mediated keratinocyte apoptosis
• “Conclusion: IVIG may be considered an effective treatment of TEN”
• In retrospective multi-center study: high-dose IVIG regimen of 0.6 g/kg/day over 4
days was given no fatality at 45 days was observed and time to complete healing
in patients receiving IVIG early was shorter
• In multi-center retrospective study on the effectiveness of high-dose IVIG (2.7 g/kg
bodyweight on average) in 48 patients survival rate was 88% at day 45
• Patients receiving IVIG in high doses in the initial stages of TEN typically showed a
better treatment response
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
69. Management - IVIG
• Systematic review and meta-analysis - no benefit in patients treated with high-dose
IVIG could be seen, in terms of mortality, the early use of IVIG compared to
patients receiving only supportive care or corticosteroids was shown to be effective
in a single center
• “Use of IVIG remains controversial, although positive effects is possible”
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
70. Management – Cyclosporine A
• In Spain-based study, disease progression stopped significantly more rapidly and
also faster complete wound healing
• “The use of CsA has a benefit in epidermal necrolysis”
• Meta-analysis showed a mortality risk ratio (MRR) of 0.14 for CsA-treated patients
• Combined plasmapheresis and CsA in TEN significantly lower mortality rate
• In children, use of IVIG and corticosteroids is controversial as well, CsA showed
promising results suggesting its use as monotherapy
• Another recent prospective observational study investigating adults and children
found that plasmapheresis may be superior to conventional therapies, also when
used alone
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
71. Management - Others
• Cyclophosphamide and thalidomide - no longer used due to ineffectiveness or
higher mortality rate
• Eternacept - too early to draw conclusions as to effectiveness and side-effects of
TNF-α antagonists
Marianne L. et al. Clinic Rev Allerg Immunol 2018; 54:147–176.
72. White et al. J Allergy Clin Immonol Pract 2018;6(1):38-69.
Acute Management
74. White et al. J Allergy Clin Immonol Pract 2018;6(1):38-69.
Chronic Management
Editor's Notes
<0, Very unlikely; 0–1, unlikely; 2–3, possible; 4–5, probable; ≥6, very probable
ATC, anatomical therapeutic chemical; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis
A Drug (or active metabolite) elimination half-life from serum and/or tissues, taking into account kidney function for drugs predominantly cleared by kidney and liver function for those with high hepatic clearance.
B Suspected interaction was considered when more than five drugs were present in a patient’s body at the same time.
C Similar drug=same ATC code up to the fourth level (chemical subgroups).
D Definitions for “high risk,” “lower risk,” and “no evidence of association” in Methods
Adapted from Sassolas B et al. ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson Syndrome and toxic epidermal necrolysis: comparison with case-control analysis. Clinical pharmacology and therapeutics 2010; 88(1): 60–68
Proposed pathogenic mechanisms in drug-induced SJS/TEN and DRESS.
The disease process in SJS/TEN occurs in the epidermis. In SJS/TEN, the drug likely interacts with the human leukocyte antigen protein on keratinocytes that act as antigen-presenting cells to activate drug-specific CD8þcytotoxic Tcells. This interaction causes drug-specific CD8þTcells to accumulatewithin epidermal blisters and release perforin and granzyme B that can kill keratinocytes. Drugs also trigger the activation of CD8þTcells, NK cells, and NKTcells to secrete granulysin, which appears to be one of the most important cytotoxic mediators in SJS/TEN and can induce keratinocyte death without the need for cell contact. Clinical symptoms of SJS/TEN include a painful, blistering skin rash that results in epidermal necrosis and detachment as well as less specific symptoms including fever and sepsis. SJS/TEN is associated with a mortality of up to 50% as well as significant long-term morbidity including permanent corneal scarring, vision loss, prolonged pain and weakness, posttraumatic stress disorder, and fear of drug.
APC, Antigen-presenting cell; CTL, cytotoxic lymphocyte; DC, dendritic cell; NK, natural killer cell; NKT, natural killer Tcell; PTSD, posttraumatic stress disorder; TCR, T-cell receptor
Suggested multidisciplinary approach to the management of (A) acute- and (B) recovery-phase SJS/TEN.
Key points highlighted include the necessity to
recognize and stop the offending medication quickly
provide care for SJS/TEN in a tertiary critical care center (most often a burn center)
Consider all organ systems involved in SJS/TEN and consult relevant subspecialists early in the disease course, and
provide posthospital and long-term follow-up for patients to manage complications of SJS/TEN.
ALDEN, Algorithm for assessment of drug causality in epidermal necrolysis; AT, artificial tears; FML, fluorometholone 0.1% ophthalmic ointment; GERD, gastroesophageal reflux disease; GI, gastrointestinal; HSV, herpes simplex virus; MF, moxifloxacin 0.5% ophthalmic solution; PA, prednisolone acetate 1% ophthalmic solution.