This document discusses drug hypersensitivity reactions and their clinical presentation and workup. It begins by outlining the pathomechanisms of drug hypersensitivity, including the hapten and p-i concepts of how drugs are recognized by the immune system. It then classifies drug hypersensitivity reactions and describes the clinical features of maculopapular rash, DRESS/DIHS, SJS/TEN, and AGEP. The document concludes by covering the allergologic workup for drug hypersensitivity, including in vivo and in vitro tests to detect drug-specific T cells.
Drug-induced hypersensitivity syndrome (DIHS)/Drug reaction with eosinophilia and systemic symptoms (DRESS)
Presented by Pongsawat Rodsaward, MD.
December 17, 2021
Drug-induced hypersensitivity syndrome (DIHS)/Drug reaction with eosinophilia and systemic symptoms (DRESS)
Presented by Pongsawat Rodsaward, MD.
December 17, 2021
Drug reaction with eosinophilia and systemic symptoms & acute generalized exanthematous pustulosis 2019
Presented by Nattasasi Suchamalawong, MD.
November 15, 2019
Drug reaction with eosinophilia and systemic symptoms & acute generalized exanthematous pustulosis 2019
Presented by Nattasasi Suchamalawong, MD.
November 15, 2019
Cross hypersensivity to NSIADs, Allergic and pseudoallergic reactions.Utai Sukviwatsirikul
Cross hypersensitivity of NSAIDs
Allergic and pseudoallergic reactions
source of info: http://www.si.mahidol.ac.th/th/division/soqd/admin/news_files/423_18_3.pdf
Presentation entitled "Drug Allergy: what have we learned from immunogenetics?", updated and published in Portuguese as an open access full-text "Santos N, Cernadas J. Imunogenética das reacções alérgicas a fármacos. Rev Port Imunoalergologia 2013;23(4):247-258."
SLE Systemic lupus erythematosus 2022
Basics, updates Prof. Hanan Ali Taha, professor of Internal Medicine and Head of the immunology unit, Faculty of Medicine, Beni-Suef University University
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)Apollo Hospitals
Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest mortality (30–35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but with less extensive skin detachment and a lower mortality (5–15%). Hypersensitivity syndrome, sometimes called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at about 10%. It is characterised by fever, rash and internal organ involvement. Prompt diagnosis is vital, along with identification and early withdrawal of suspect medicines and avoidance of re-exposure to the responsible agent is essential. Cross-reactivity to structurally-related syndrome caused by Carbamazepine medicines is common, thus first-degree relatives may be predisposed to developing this syndrome. We report a case of DRESS secondary to use of Carbamazepine.
Arthritis (Rheumatoid Arthritis, Osteoarthritis, Gout)
PPT contains content for UG healthcare students.
Elaborated topics referred from Nursing books, Orthopedics books, and some live cases from the department.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
3. How drugs are recognized by the
immune system?
Pathomechanism
4. Hapten and prohapten concepts and noncovalent drug
presentation to T cells
Med Clin N Am 94 (2010) 645–664
5. Acylation of lysine residues in serum or cell surface proteins results in penicilloyl or major
antigenic determinant. From its isomer penicillanic acid, other covalent linkages to
macromolecules can occur to produce a variety of less common and/or less dominant ‘minor’
epitopes.
Middleton’s allergy. Seventh edition.
6. Sulfonamide metabolism and haptenation. Sulfonamides are metabolized by N4-oxidation by
cytochrome P450 enzymes or by N4-acetylation. N-acetyl sulfonamides and glutathionyl
(GSH) sulfonamides are then excreted. Free sulfonamides, N-acetyl sulfonamides, and GSH
sulfonamides have the potential to act as univalent inhibitors of antibody-mediated reactions.
Carrier haptenation can occur after N-oxidation if the capacity for GSH conjugation is
exceeded
Middleton’s allergy. Seventh edition.
7. The p–i concept of T lymphocyte activation. The drug happens to fit into some TCR (1) with sufficient affinity
to cause a signal. This drug-TCR interaction is supplemented by MHC interaction (2). The T cells react and
proliferate. No metabolism of drugs required. The reactive T cell is probably preactivated and has an
additional peptide specificity.
Middleton’s allergy. Seventh edition.
8. Evidence for p-i mechanism :
◦ Aldehyde-fixed APC are still able to activate specific TCC if
incubated together with drug
◦ drug binding to proteins more labile than covalent interactions
of haptens and can be washed away
◦ Calcium influx in TCC happens within seconds ; before drug
uptake, metabolism, and processing can occur
clinical features of p-i concept are as
follows:
◦ Positive skin test reactions to inert drugs, although no
cutaneous metabolism of this peculiar drug is known
◦ Immune reactivity at first encounter, without time of sensitization
◦ Higher risk in viral infections, to lower threshold for T cell
reactivity
◦ Fulminant course (as with superantigen stimulations)
◦ reflects abnormal T-cell stimulation with massive/fatal self-
destruction as seen in SJS/TEN and DRESS/DiHS
Med Clin N Am 94 (2010) 645–664
12. Characteristic chronology of drug-induced eruptions.
separation at 1 hour into immediate or nonimmediate reactions not
sufficiently reflect large overlap between pathophysiologically
determined immediate- and delayed-type clinical manifestations
Med Clin N Am 94 (2010) 711–725
13. Revised Gell and Coombs classification of drug
reactions
Med Clin N Am 94 (2010) 645–664
14. T cell orchestrated hypersensitivity reactions
(Gell and Coomb's types IVa–d)
Middleton’s allergy. Seventh edition.
16. Maculopapular or morbilliform exanthema
most common
initially with erythematous
macules and infiltrated papules,
affecting particularly trunk and
proximal ext.
(Classic) appear after 7 to 10
days
DDx : classic infectious
exanthems eg. measles and
rubella
In more severe reactions,
elevated eosinophil counts (~ 50%
of pts.)
Common elicitors : ATB
(aminopenicillins and quinolones),
antiepileptic drugs, RCM
First signs eg. discrete erythema
may even appear after a few
Med Clin N Am 94 (2010) 665–679
hours
17. Systemic danger signs for severe delayed-type
reactions
Fever
Malaise
Prolonged clinical symptoms after
discontinuation of the causative drug
Lymphadenopathy
Eosinophilia >1.5* 109 cells /liter
Liver involvement
Med Clin N Am 94 (2010) 665–679
19. Central facial erythematous swelling in
DRESS syndrome (left), SJS (middle), and
TEN (right) (diffuse erythematous swelling)
Med Clin N Am 94 (2010) 681–689
20. Atypical target lesions( SJS/TEN )
Typical target lesions
< 3 cm in diameter with a only 2 zones, are mostly
regular round shape, flat, and irregular shape
well-defined border, and darker color and
2 concentric rings around sometimes central
a central disk blister
Med Clin N Am 94 (2010) 681–689
21. Positive Nikolsky sign in edematous,
erythematous skin indicating necrolytic
detachment of epidermis in SJS/TEN
Med Clin N Am 94 (2010) 681–689
22. Severe mucositis in a patient with TEN,
manifesting >1 day before epidermolysis of
skin was detectable
Med Clin N Am 94 (2010) 681–689
23. Cutaneous danger signs for severe delayed-
type reactions
Involvement of large body surfaces or
erythroderma
Painful skin, skin tender to touch
Hemorrhagic necrotizing lesions
Purpura
Med Clin N Am 94 (2010) 681–689
24. Clinical symptoms and laboratory
findings of DIHS/DRESS
Med Clin N Am 94 (2010) 743–759
25. Face swelling in early manifestation of
DRESS syndrome
occurs in 1 in 1,000 -
10,000 exposures to
antiepileptic drugs
2 -12 weeks after
initiation of specific
drug therapy
Mortality ~ 10%
anticonvulsants,
dapsone, allopurinol,
and minocycline
DDx : viral infection
( EBV, CMV ),
autoimmune
Med Clin N Am 94 (2010) 691–710
26. Diagnostic criteria for DRESS
MP rash developing > 3 weeks after starting with
drugs
Prolonged clinical symptoms after discontinuation of
causative drug
Leukocyte abnormalities (at least 1 present):
◦ Leukocytosis (>11 * 109 cells / liter)
◦ Atypical lymphocytosis (>5%)
◦ Eosinophilia (>1.5 * 109 cells / liter)
Lymphadenopathy
Fever (>38ºC)
Liver abn. (ALT >100 U/L) or other organ
involvement
HHV 6 reactivation (during 2nd to 3rd week after start
Med Clin N Am 94 (2010) 665–679
of symptoms)
27. Time interval between onset and visceral
involvements during course of DIHS/DRESS
Med Clin N Am 94 (2010) 743–759
28. Visceral organ involvements in acute stage
Hepatitis
◦ most common (~70%)
◦ If icteric, poorer prognosis
◦ Coagulopathy in severe case
◦ Steroid benefit in fulminant hepatitis
◦ In Europe, 1 mg/kg/d of prednisolone recommended, if ALT >500 IU, Tapering
according to clinical course, too early CS reduction tends to transient
exacerbations
◦ NAC ( case report, 24g/d over 3 d )
Nephritis
◦ ~11%
◦ kidney biopsy : AIN with lymphocytic infiltrate and ATN ( case SSZ )
Hemophagocytic syndrome (HPS)
◦ Rare
◦ triggered by viral infection, malignant tumors, or autoimmune diseases
Myocarditis
◦ Rare
Med Clin N Am 94 (2010) 743–759
31. SJS and TEN
incidence of TEN 1.89 cases per million
per year
Genetic susceptibility
◦ HLA-B*1502, SJS, carbamazepine in Han
Chinese ( OR =2504 ), not in Europe
◦ HLA-B*5801, SJS and TEN , allopurinol
(OR= 80) independent of ethnic background
differential diagnoses
◦ EM major
◦ Autoimmune bullous disorder: Linear IgA
bullous dermatosis, BP, paraneoplastic
pemphigus
◦ SSSS
Am J Clin Dermatol 2003.
32. Clinical features that distinguish
SJS, SJS-TEN overlap, and TEN
Med Clin N Am 94 (2010) 727–742
33. Drugs with high risk of inducing SJS/TEN
Antibiotics
◦ TMP/SMX
◦ Aminopenicillin
◦ Cephalosporin
◦ Quinolone
Anticonvulsant
◦ Carbamazepine
◦ Phenytoin
◦ Phenobarbital
Nevirapine
Oxicam-NSAID
Allopurinol(most common in Europe and Israel
) Med Clin N Am 94 (2010) 727–742
34. Management and Therapy
Prompt withdrawal of culprit drugs and
supportive care
Drug therapy , specific therapy does not
exist
High-dose IVIg
◦ 8 /11 studies may be benefit of IVIG used (>2
g/kg over 3 to 4 days ) on mortality ( TEN )
CsA : insufficient to draw conclusions
Systemic steroid : remains controversial
prevention of ocular complications
Med Clin N Am 94 (2010) 727–742
35. SCORTEN severity-of-illness score
SCORTEN Parameter Individual SCORTEN (Sum Predicted
Score of Individual Mortality
Scores) (%)
Age>40 years Yes = 1, No = 0 0–1 3.2
malignancy Yes = 1, No = 0 2 12.1
Tachycardia (>120/min) Yes = 1, No = 0 3 35.8
Initial surface of Yes = 1, No = 0 4 58.3
Epidermal detachment >10%
Serum urea >10 mmol/L Yes = 1, No = 0 5 90
( 28 mg/dl )
Serum glucose >14 mmol/L Yes = 1, No = 0
(252 mg/dl )
Bicarbonate <20 mmol/L Yes = 1, No = 0
Med Clin N Am 94 (2010) 727–742
Average mortality : SJS 1- 5%, and TEN 25- 35%
36. Acute generalized exanthematous
pustulosis
5 cases per million
annually
females > males
mean age 56 years
Treatment
◦ Exclude infectious dis.
◦ intermediate to high
doses of systemic
corticosteroids over
several days
◦ local corticosteroids of
high potency applied
for 5 - 10 days
Med Clin N Am 94 (2010) 727–742
37. Differential diagnoses of
AGEP
Generalized pustular psoriasis
Subcorneal pustulosis
Subcorneal IgA dermatosis
Infectious folliculitis
Viral exanthema with secondary
pustulation
Sweet syndrome(neutrophilic dermatosis )
Med Clin N Am 94 (2010) 727–742
38. Drugs with high risk for induction of
AGEP
Ampicillin/amoxicillin
Pristinamycin
Quinolone
Anti-infective sulfonamides
Terbinafine
Hydroxychloroquine
Diltiazem
Med Clin N Am 94 (2010) 727–742
42. Tests for detection of drug-specific T cells in
patients with delayed-type drug
hypersensitivity
Immunol Allergy Clin N Am 29 (2009) 537–554
43. Guidelines in drug skin testing
performed 6 weeks to 6 months after
complete healing of CADR
at least 1 month after discontinuation
of systemic corticosteroid or
immunosuppressive therapy
not to test during pregnancy
Contact Dermatitis, 2001, 45, 321–328
44. Drug Patch Testing
performed on upper back using Finn Chambers
read at 20 min, D2 and D4 ,D7 (if negative on D4)
In FDE, should be performed both on normal skin
and on residual pigmented site of FDE
with commercialized drug
◦ Incorporated at 30% in pet. and aq.
◦ made for only 1 patient and kept no > 1 D
with pure substances
◦ diluted at 10% in pet.& aq. or alcohol (alc.).
aciclovir, carbamazepine or pseudoephedrine
◦ first diluted at 0.1% and 1,10% ( in severe CADR)
Contact Dermatitis, 2001, 45, 321–328
45. Drug Patch Testing
value in generalized eczema, systemic
contact dermatitis, baboon syndrome, MP
rash , AGEP , lichenoid rash and fixed
drug eruption
less value in SJS, TEN, pruritus or
vasculitis
most frequent reports of positive patch
tests
◦ Betalactam esp. amoxicillin, Cotrimoxazole
◦ corticosteroids , heparin derivatives ,2001, 45, 321–328
Contact Dermatitis,
47. Drug Patch Testing
Negative results :
◦ drug metabolite not formed in skin
◦ no immune mechanism
◦ No concomitant factors eg. Viral infection
Best vehicle not yet been determined
◦ steroid hormone (in alcohol)
◦ Corticosteroid ( in water& alcohol)
◦ Ganciclovir ( in water )
Positive results vary (10-60%)
Contact Dermatitis, 2001, 45, 321–328
48. Intradermal Tests (IDT)
Contraindicated in SJS, TEN or LCV
diluted sequentially (10-4, 10-3, 10-2 and 10-1) in
phenolated saline or in 0.9% saline
performed on extensor surface of arm, with
small volume (0.04 ml) produces weal (4-6
mm)
Readings performed at 30 min, 6 h and 1 D (
1 week, if result are negative )
risk of eliciting relapse of initial CADR ( 3
minor incidents/30)
Contact Dermatitis, 2001, 45, 321–328
49. Intradermal test results positive for Patch test results positive for AX
AX and AM and AM
Nonimmediate skin test results
Med Clin N Am 94 (2010) 805–820
50. Drugs Patch test Intradermal test
Aminopenicillins 10% in Pet. 20-25 mg/ml
Cephalosporins 10% in Pet. 1/10 of full strength
Pristinamycin 10% in Pet.
Quinolone 30% in Pet. Or water 1/100 of full strength
Co-trimoxazole 10% in Pet. 1/100 of full strength
Minocycline 10% in Pet.
Carbamazepine 1%,10% in Pet.
NSAIDs (oxicams) 1%,10% in Pet.
51. Lymphocyte Transformation
Test
most widely used test
principle : simple proliferation test with Ag
useful in MPE, pustular exanthema, bullous
exanthema and DRESS
cultured in presence of suspected drug for 6
days
measured by incorporation of 3H-thymidine
during DNA synthesis
stimulation index (SI) >2 ( 3 for betalactam )
not necessarily associated with clinical
severity
Sensitivity 60- 70% (depends on drug tested,
Immunol Allergy Clin N Am 29 (2009) 537–554
> skin test )
52. Lymphocyte Transformation
Test
Specificity ~ 85%
Perform in 1-6 mo. After event ( bullous
dis., positive in first week of dis.)
False positive :vancomycin, possibly
paracetamol, and RCM
False negative :abacavir
disadvantages:
◦ requires sterile cell cultures
◦ takes a long time and cumbersome
◦ depends on quality of culture medium
◦ involves radioactivity, and expensive
equipment
Immunol Allergy Clin N Am 29 (2009) 537–554
53. CD69 UP-REGULATION
CD69 : membrane type II C-type lectin,
transiently expressed on activated
lymphocytes
up-regulated in T cells from patients who
had drug-induced MPE, erythema
multiforme, SJS, and DRESS when
assessed by flow cytometry
comparable to LTT
Advantage : not require radioactive
substances and less time-consuming
Disadvantage : flow cytometry-based
test, difficult to standardize
Immunol Allergy Clin N Am 29 (2009) 537–554
55. Measurement Of Drug-induced Cytokine
Production From Ex Vivo PBMC
measurement of IL-2, IL-5, IL-13, and IFN-γ
cytokines might be promising tool for detecting
drug sensitization in delayed-type reactions
ELISA or ELISPOT assay, or multiplexed bead-
based flow cytometric assays, mRNA by RT-
PCR
IFN-γ ELISPOT assay exhibited high sensitivity
and specificity since specific T cells were
detected in 20/22 ( 91%) of amox-DTH patients
only 1/26 nonDTH allergic patient had
unexpected but weak reactivity to unrelated
control antibiotic
Immunol Allergy Clin N Am 29 (2009) 537–554
Allergy 2009: 64: 534–542
56. ELISA ELISPOT
Immunol Allergy Clin N Am 29 (2009) 537–554
57. Cytotoxicity: Granzyme B Enzyme
Immunospot Assay
gives results 48 to 72 hours after stimulation
and not involve radioactivity
Once cytotoxic T cells get activated, lytic
granules reach plasma membrane,
granzymes and perforin released into
immunologic synapses, and cumulative
exposure of granular membrane proteins
(CD107a) can be measured on surface of
responding cytotoxic cells, providing positive
marker for degranulation
seems to be most sensitive and robust
method to detect cytotoxic cells in peripheral
blood of drug-allergic patients
Immunol Allergy Clin N Am 29 (2009) 537–554
59. When Should Diagnostic Tests Be
Performed?
recommend performing LTT within 1 week
after onset of skin rashes in MP eruptions
and SJS or TEN and > 5 to 8 weeks after
event in DRESS
some patients lose reactivity within 1 to 3
years after reaction
many groups carry out tests after of 3 weeks-
6 months after acute event
In vitro tests offer advantage of safety,
simultaneous assessment of T-cell responses
to multiple drugs, lack of risk for
resensitization, and insight into
pathomechanism
Immunol Allergy Clin N Am 29 (2009) 537–554
60. Conclusion
Delayed type drug hypersensitivity
classified by pathomechanism (type IVa-
d)
MP rash : most common
SJS/TEN : most severe, treatment is
supportive care ( may be try IVIg )
Skin test ( patch test, ID test ): low
sensitivity
In vitro test : LTT ( gold standard ), other
test remained study
rigid separation between immediate and nonimmediate reactions at 1 hour based on the chronology only may be problematic, because there is a considerable overlap of a period of approximately 2 to 6 hours between the reaction period of urticarial and exanthematous eruptions (see Fig. 2, Table 1). The terms immediate and delayed are also commonly used to depict the pathophysiology (ie, type I [IgE mediated]and type IV [T cell mediated]). This is most important with regard to the selection of appropriate diagnostic tests
Type IVa reactionscorrespond to Th1 reactions with high IFNg/TNFa secretion, and involve monocyte/macrophageactivation. CD8 cell recruitment (type IVc reaction) often occurs. Type IVb reactionscorrespond to eosinophilic inflammation and to a Th2 response with high IL-4/IL-5/IL-13secretion; they are often associated with an IgE-mediated type I reaction. Type IVc reactions:the cytotoxic reactions (by CD4 and CD8 cells) rely on cytotoxic T cells as effector cells (type IVc). They seem to occur in all drug-related delayed hypersensitivity reactions. Type IVd reactions correspond to a T-cell–dependent, sterile neutrophilic inflammatory reaction. It is distinct from the rapid influx of PMN in bacterial infections. It seems to be related to high CXCL-8/GM-CSF production by T cells
Erosive stomatitis; mucositis, especially if affecting more than one mucosa
typical dermoepidermal detachment and necrosis beneath the stratum corneum in SJS/TEN
Provocation test not well standardized in delayed reactions regarding dose, durationof symptoms, and definition of positivity, and are therefore difficult to perform
International Contact Dermatitis Research GroupIrritant reaction Controls show similar response or there was an excited skin responseDoubtful reaction Negative test result. Repeat readings at 3, 4, and 7 days after patch removed. If ACD still suspected, recheck technique or do ROAT1+Light erythema, nonvesicular Equivocal test result. Could either be negative or indicative of waning prior sensitization. False-positive test result or excited skin syndrome must be ruled out by test in control subject. Repeat steps in 3.2+ Edema, erythema, discrete vesicles Positive test result. Indicative of prior or current sensitization. Should correlate with history and physical findings. False-positive test result or excited skin syndrome must be ruled out by test in control subject3+ Coalescing vesiculobullous papules Strongly positive result.
(0.5% phenol in 0.9% saline)
large prospective study is required to evaluate this test and to determine sensitivity and specificity in drug hypersensitivity diagnosisThis prospective study is currently being performed by the authors’ drug allergy research group in Bern
necessary to evaluate anaccurate cutoff for positivity and the exact sensitivity and specificity of these assays