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Approach to a patient with Exanthem
Dr Sanjay Singh
Exanthem
 Non scaly maculopapular rash which can encompass other abruptly appearing lesions
such as papules, pustules & v...
• 6 Classic Exanthem
First disease : Measles (Rubeola)
Second disease : Scarlet fever
Third disease : German measles (Rube...
The challenge of diagnosing atypical exanthems: a clinico-
laboratory study.
Drago F, Paolino S, Rebora A et al. J Am Acad...
Assessment of Maculopapular Exanthem
• Skin eruption consisting of macules and papules which does not form scale
Classific...
Maculopapular Drug Exanthem
 When clinical presentation is Maculopapular rash, the cause is drug induced in 50% to
70% of...
Clinical Findings
 Dusky red macules predominate initially, then become confluent patches with
papular areas within
 Sym...
 Drug eruption participants : 1317
 Maculopapular exanthem : 1201 (91.11 %)
 Most common implicated drugs
Penicillin
Su...
DRESS syndrome
Drug rash with eosinophilia and systemic symptoms
 Hypersensitivity syndrome develops 2 to 6 weeks after d...
MC (and usually most severe) site of visceral involvement is liver & is responsible for
majority of deaths associated with...
Diagnostic criteria for drug-induced hypersensitivity syndrome (DIHS)
established by a Japanese consensus group
Maculopapu...
Viral Exanthem
Clinical features suggestive of viral exanthem
 Fever with or without constitutional symptoms
 Patterned ...
 Enanthem – in most cases associated with viral exanthem
 Rash is self limiting – usually subsides spontaneously within ...
Season Characteristics of Rash Enanthem Characteristic
Features
Measles Late winter
/spring
Begin on forehead, hairline an...
Koplik’s spot Forschheimer’s spots
Nagayama spots
Measles
Erythema
infectiosum
Measles Rubella Erythema infectiosum
Epstein Barr Virus
 Human Herpes Virus 4
 MC age group affected : 14 – 25Y
 Incubation Period : 4 to 8 weeks
 Preferen...
Clinical Findings
Triad of fever, lymphadenopathy, and pharyngitis develops in 80% of cases
Rash begins on day 4 to 6 of i...
Spectrum of Infectious Mononucleosis
EBV and ampicillin/amoxycillin
 Complex Interaction between drug and virus
 Generalised copper-coloured eruption in most...
Copper-colored maculopapular rash on trunk and extremities after
taking oral amoxicillin in a patient of infectious mononu...
Complications
• Dehydration (due to severe pharyngitis)
- Streptococcal pharyngitis: 25% G-A strep infection
- Splenic rup...
Coxsackievirus, echovirus, and enterovirus
 Most common cause of viral exanthem
 Transmitted by the faecal-oral or respi...
Hepatitis & HIV
During the viraemic phase of acute infection
Primary HIV infection : 10% to 12% will develop an acute synd...
MC arthropod-borne viral (arboviral) illness in humans
Transmitted by mosquitoes of the genus Aedes
Characteristic exanthe...
Dengue Rash
Kawasaki disease
 Acute multi-system febrile disease
 Peak incidence : children 2 years of age and younger, and 85% of p...
Ulceration at the site of BCG vaccination is one of specific feature
Perineal erythema is particularly pronounced which of...
Kawasaki disease
Perineal Erythema on 2nd day of fever Desquamation after 2 days
Edema of Hands Periungual Desquamation
Oropharyngeal Changes : Dry, fissured lips
Strawberry tongue
Diffuse hyperaemia of the oral mucous membrane
Cardiac Involv...
Cheilitis Strawberry Tongue
Fever for 5 days plus 4 of the following 5 :
1) Bilateral non-purulent conjunctival injection
2) Cervical lymphadenopathy ...
Bacterial Exanthems
Meningococcemia
Close living conditions such as college dormitories, prisons, military barracks
Poor Immune status ( Young...
Clinical Findings
May start as transient, blanchable macular erythema on the extremities
1/3rd to 1/2 of patients present ...
Purpuric Lesion
RICKETTSIAL INFECTIONS
Summer/autumn incidence corresponding with outdoor activities and
with possible tick exposure
Antec...
Cutaneous Features
Eschar formation
Central area of dermal and epidermal necrosis (0.5–2 cm)
surrounded by a zone of eryth...
3 to 6 days
Petechiae and Purpura in generalized distribution
Rash begins as erythematous macules around the wrists and an...
Eschar
Dusky red maculopapular rash over ankle Multiple purpuric lesions
Toxin Mediated Bacterial Infections
 Toxin produced by group A beta-haemolytic Streptococcus, typically following pharyng...
 Eruption begins 12–48 hours later as blanchable erythema on the neck, chest and axillae
 Subsequent generalization and ...
Strawberry tongue : initially white with bright red papillae, later becomes beefy red
Throat is red and edematous, develop...
sandpaper-like texture Pastia’s lines
Staphylococcal Scalded Skin Syndrome
 Caused by exfoliative toxins ET-A and ET-B
 Toxins target granular layer of epider...
 Erythema begins on the head and rapidly (hours) generalises
 Skin becomes swollen, and fragile superficial vesicles and...
Toxic shock syndrome
Caused by Staphylococcus aureus exotoxin (TSS-toxin-1)
TSS is characterised by high fever (>39.6°C), ...
• Clinical Criteria
• An illness with the following clinical manifestations :
• Fever ≥ 102.0°F
• Rash: diffuse macular er...
Macular Erythema Conjuctival suffusion
Desquamation Of Palms
Post Transplantation : Acute GVHD
Sudden onset of maculopapular exanthema occurs 1 to 3 weeks after transplant
Can appear ...
Pruritus is variable and a follicular pattern may be observed
Severe cases : Diffuse erythroderma and desquamation, and mu...
CLINICAL STAGING OF ACUTE GRAFT-VERSUS-HOST DISEASE
Stage Skin
Maculopapular
Exanthem
Liver
(Bilirubin)
Gut
Diarrhea
Grade...
Investigations
Drug Exanthem
 Maculopapular Drug Rash
 DRESS Syndrome
TLC, DLC & Peripheral Blood Smear
LFT/RFT
 DRESS syndrome
Viral Exanthem
 Haemogram with Peripheral Blood smear
Serology
• Viral Exanthem : IgM antibodies
• Infectious Mononucleos...
Bacterial Exanthem
Platelet count
LFT/RFT
 Toxic shock syndrome
ASO titre : Scarlet Fever
PCR & Culture : Scarlet fever
M...
Histopathology & Immunohistochemistry
Primary changes of maculopapular drug eruptions are -
 Inter and intracellular edema as well as disruption of epidermal b...
 Interface dermatitis with superficial, mainly perivascular infiltrate of CD4 T-cells
 CD4 and CD8 T-cells in equal numb...
Histologic features of most drug eruptions are not entirely specific
Superficial infiltrates composed variably of L, N and...
Epidermis of drug exanthem patients showed infiltration of CD4>CD8 cells
Marked enhancement of perforin and granzyme B imm...
Most common pattern of drug eruption is vacuolar interface dermatitis.
Sparse P/V & interstitial infiltrate of N, Eo with ...
Role of Immunohistology
Soluble FAS ligand: a discriminating feature between drug-induced
skin eruptions and viral exanthe...
Levels of sFASL in diseases of comparison groups
Diseases Quantity sFASL (ng/ml) %
Chickenpox 11 Negative 0
Shingles 11 Ne...
Based on FAS-ligand staining on tissue specimen
Fas-ligand staining in non-drug- and drug-induced maculopapular rashes.
Wa...
Maculopapular Drug Exanthem Maculopapular Viral Exanthem
Evidence for a role for IL-5 and eotaxin in activating and recruiting
eosinophils in drug-induced cutaneous eruptions.
Yaw...
Staphylococcal Scalded Skin Syndrome
Acute GVHD
Algorithm to a patient with
Maculopapular Exanthem
Maculopapular Rash
Drugs
Tender Rash
with
mucosal
erosions
Infectious
Miscellaneous
Non Infectious
Inflammatory
Cause
Char...
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rash, exanthem, approach to exanthem, maculopapular exanthem, Exanthem seminar, Fever and Rash, Approach to patient with maculopapular exanthem

  1. 1. Approach to a patient with Exanthem Dr Sanjay Singh
  2. 2. Exanthem  Non scaly maculopapular rash which can encompass other abruptly appearing lesions such as papules, pustules & vesicles & affecting several areas simultaneously  Greek origin “exanthema” which means “a breaking out”  Poorly defined in literature, few literature restrict exanthem as maculopapular rash  Enanthem (enanthema) : An eruption upon a mucous membrane
  3. 3. • 6 Classic Exanthem First disease : Measles (Rubeola) Second disease : Scarlet fever Third disease : German measles (Rubella) Fourth disease : Duke’s Filatow disease (scarlet fever variant) Fifth disease : Erythema infectiosum Sixth disease : Roseola, Erythema subitum  All other exanthems are broadly described as atypical exanthems
  4. 4. The challenge of diagnosing atypical exanthems: a clinico- laboratory study. Drago F, Paolino S, Rebora A et al. J Am Acad Dermatol. 2012 Dec;67(6):1282-8. • Seven Morphological Pattern Macular erythema Papular erythema Macular-papular erythema Erythematovesicular Macular-papular erythema with petechiae Erythema with pustules Urticarial
  5. 5. Assessment of Maculopapular Exanthem • Skin eruption consisting of macules and papules which does not form scale Classification of Maculopapular Exanthem Drugs Infections Unknown ? Infectious Non – Infectious Inflammatory Miscellaneous Maculopapular Drug Rash Viral Kawasaki ds Familial inflamm. syndromes Acute GVHD Dress Syndrome Bacterial Still’s ds AILD SJS - TEN Rickettsial
  6. 6. Maculopapular Drug Exanthem  When clinical presentation is Maculopapular rash, the cause is drug induced in 50% to 70% of adults and 10% to 20% of children  Develop within days to weeks (usually within 4 to 12 days) after initiation of a novel drug and usually last up to 2 weeks after cessation of the culprit medication  Common drugs responsible are antibiotics such as penicillins, quinolones, and sulfonamides, anticonvulsants, allopurinol, and NSAIDs Bolognia textbook of Dermatology
  7. 7. Clinical Findings  Dusky red macules predominate initially, then become confluent patches with papular areas within  Symmetric distribution of rash – usually starting from trunk extending towards extremities but face may be spared.  Moderate to Severe pruritus  Mucous membranes are typically spared  Eruption generally fades over 1 to 2 weeks after discontinuation of drug  Post-inflammatory desquamation is common
  8. 8.  Drug eruption participants : 1317  Maculopapular exanthem : 1201 (91.11 %)  Most common implicated drugs Penicillin Sulfonamides NSAIDS  Development of Rash : 1-12 days Comprehensive hospital drug monitoring (CHDM): adverse skin reactions, a 20-year survey. Hunziker T, Kunzi UP, Braunschweig S et al. Allergy 1997 Apr;52(4):388-93.
  9. 9. DRESS syndrome Drug rash with eosinophilia and systemic symptoms  Hypersensitivity syndrome develops 2 to 6 weeks after drug initiation  Fever and cutaneous eruption are most common symptoms  Cutaneous involvement usually begins as morbilliform eruption, which later becomes edematous, often with follicular accentuation.  Edema of face is frequent finding and is hallmark of DRESS
  10. 10. MC (and usually most severe) site of visceral involvement is liver & is responsible for majority of deaths associated with this syndrome Every organ system can be affected Important implicated drugs : Aromatic anticonvulsants (phenobarbital, carbamazepine and phenytoin) Lamotrigine Sulfonamides Minocycline Allopurinol
  11. 11. Diagnostic criteria for drug-induced hypersensitivity syndrome (DIHS) established by a Japanese consensus group Maculopapular rash developing > 3 weeks after starting with suspected drug Prolonged clinical symptoms 2 weeks after discontinuation of suspected drug Fever (> 38˚C) Liver abnormalities (alanine aminotransferase > 100 U⁄ L)* Leucocyte abnormalities : Leucocytosis (> 11 × 109 ⁄ L) Eosinophilia (> 1.5 × 109 ⁄ L) Atypical lymphocytosis (> 5%) Lymphadenopathy Human herpesvirus 6 reactivation 7 Criteria : Typical DRESS 5 Criteria : Atypical DRESS
  12. 12. Viral Exanthem Clinical features suggestive of viral exanthem  Fever with or without constitutional symptoms  Patterned distribution  Asymptomatic to mild pruritus
  13. 13.  Enanthem – in most cases associated with viral exanthem  Rash is self limiting – usually subsides spontaneously within 7 days  Usually affects children  Maculopapular rash with petechie - in most cases associated with viral exanthem  Seasonal clustering of cases
  14. 14. Season Characteristics of Rash Enanthem Characteristic Features Measles Late winter /spring Begin on forehead, hairline and behind the ears and then spread in a cephalocaudal direction. On the fifth day, the exanthem starts to fade in the same order as it appeared Koplik’s spots Rubella Late winter /spring Rose-pink macules with cephalocaudal spread Forschheimer’s spots Lymphadenopathy (retroauricular and suboccipital). Arthritis and arthralgias (adult) Erythema infectiosum Winter / spring Bright red macular erythema of cheeks Lacy, reticulated erythematous macules and papules on the extremities and (to a lesser extent) the trunk Erythema over cheeks Mild Prodrome Arthralgia Aplastic crisis Exanthem subitum No seasonal variation Discrete non-confluent rash appears when fever disappears Onset in thorax and trunk, progress to face and limbs. Nagayama spots Uvular and palatoglossal junctional ulcer Seizures occur during febrile period in up to 10% of patients
  15. 15. Koplik’s spot Forschheimer’s spots Nagayama spots
  16. 16. Measles Erythema infectiosum
  17. 17. Measles Rubella Erythema infectiosum
  18. 18. Epstein Barr Virus  Human Herpes Virus 4  MC age group affected : 14 – 25Y  Incubation Period : 4 to 8 weeks  Preferentially affects oropharyngeal mucosa and is transmitted primarily through infected saliva.
  19. 19. Clinical Findings Triad of fever, lymphadenopathy, and pharyngitis develops in 80% of cases Rash begins on day 4 to 6 of illness, initially on the trunk and upper extremities Forearms and face, with petechiae commonly present
  20. 20. Spectrum of Infectious Mononucleosis
  21. 21. EBV and ampicillin/amoxycillin  Complex Interaction between drug and virus  Generalised copper-coloured eruption in most patients  Occurs 1 week after taking the medicine and is related to EBV antibodies cross- reacting with the drug  10 % of children with Infectious mononucleosis develop an exanthem, administration of ampicillin or amoxicillin causes exanthem in 80-100 % cases  Exanthem is not reproducible after re-exposure to drug after subsidence of infection Viral exanthems in childhood. Part 3: Parainfectious exanthems and those associated with virus-drug interactions. Fölster-Holst R, Kreth HW. Dtsch Dermatol Ges. 2009;7(6):506-10.
  22. 22. Copper-colored maculopapular rash on trunk and extremities after taking oral amoxicillin in a patient of infectious mononucleosis
  23. 23. Complications • Dehydration (due to severe pharyngitis) - Streptococcal pharyngitis: 25% G-A strep infection - Splenic rupture  hemorrhage  shock death. Rupture occurs between 4th /21th day after onset of symptoms. - Chronic fatigue syndrome - Hepatitis frequently accompanies IM. High liver enzymes, hepatomegaly
  24. 24. Coxsackievirus, echovirus, and enterovirus  Most common cause of viral exanthem  Transmitted by the faecal-oral or respiratory routes  More common in summer  Incubation Period : 3 to 6 days  Rash is typically generalised and maculopapular, with petechiae, oral erosions, and conjunctival haemorrhage  Fever and pharyngitis are common
  25. 25. Hepatitis & HIV During the viraemic phase of acute infection Primary HIV infection : 10% to 12% will develop an acute syndrome 3 to 6 weeks after exposure. Syndrome includes a morbilliform eruption, fatigue, malaise, headache, and myalgia.
  26. 26. MC arthropod-borne viral (arboviral) illness in humans Transmitted by mosquitoes of the genus Aedes Characteristic exanthem in 50-82% of patients with DF After incubation period of 3–8 days, pt. develops nausea, vomiting, headaches, biphasic fever, severe myalgias, arthralgia and retro-orbital pain Rash : Morbilliform or scarlatiniform, with some areas of sparing (“white islands in a sea of red”) Minor hemorrhagic manifestations can occur, including petechiae, epistaxis and gingival bleeding; severe hemorrhage is rare Dengue Fever
  27. 27. Dengue Rash
  28. 28. Kawasaki disease  Acute multi-system febrile disease  Peak incidence : children 2 years of age and younger, and 85% of patients are <5 years of age  More common in children of Asian descent  Rash is typically generalised and maculopapular, rarely EM - like, urticarial, scarlatiniform or pustular lesion can develop.  Vesiculobullous lesions, crusting and petechiae are all unusual in the exanthem of KD.
  29. 29. Ulceration at the site of BCG vaccination is one of specific feature Perineal erythema is particularly pronounced which often desquamates within 48 hours Edema and brawny induration of the hands and feet are common early in course of disease, with eventual desquamation that is prominent in the periungual regions Eye Changes : Conjunctival injection, typically bulbar with sparing of the limbus Keratitis and photophobia are uncommon and should suggest an alternative diagnosis
  30. 30. Kawasaki disease Perineal Erythema on 2nd day of fever Desquamation after 2 days
  31. 31. Edema of Hands Periungual Desquamation
  32. 32. Oropharyngeal Changes : Dry, fissured lips Strawberry tongue Diffuse hyperaemia of the oral mucous membrane Cardiac Involvement : Coronary aneurysm (Most common cause of death) Myocarditis Congestive Heart failure Multi-organ involvement is common and affects the CNS, eyes, kidney, and GI system Vasculitis of small and medium-sized vessels contributes to the pathology
  33. 33. Cheilitis Strawberry Tongue
  34. 34. Fever for 5 days plus 4 of the following 5 : 1) Bilateral non-purulent conjunctival injection 2) Cervical lymphadenopathy (usually unilateral) 3) Oropharyngeal changes (including hyperaemia, oral fissures, strawberry tongue) 4) Peripheral extremity changes (including desquamation of hands and feet, erythema, oedema) 5) Polymorphous rash Diagnostic criteria
  35. 35. Bacterial Exanthems
  36. 36. Meningococcemia Close living conditions such as college dormitories, prisons, military barracks Poor Immune status ( Young children, Older people, splenectomy) History of Travel
  37. 37. Clinical Findings May start as transient, blanchable macular erythema on the extremities 1/3rd to 1/2 of patients present with a petechial eruption, typically in association with fever, chills, myalgias and headache Retiform purpura and ischemic necrosis may follow
  38. 38. Purpuric Lesion
  39. 39. RICKETTSIAL INFECTIONS Summer/autumn incidence corresponding with outdoor activities and with possible tick exposure Antecedent tick bite or tick attachment is made in 45% to 60% of cases
  40. 40. Cutaneous Features Eschar formation Central area of dermal and epidermal necrosis (0.5–2 cm) surrounded by a zone of erythema appears Tick / Mite / Flea bite 4–10 days
  41. 41. 3 to 6 days Petechiae and Purpura in generalized distribution Rash begins as erythematous macules around the wrists and ankles (spotted fevers) or axillae (typhus fevers) Spreads on most of the body, often with relative sparing of the face
  42. 42. Eschar
  43. 43. Dusky red maculopapular rash over ankle Multiple purpuric lesions
  44. 44. Toxin Mediated Bacterial Infections  Toxin produced by group A beta-haemolytic Streptococcus, typically following pharyngitis or tonsillitis.  MC in young children (80% of children have antibodies by 10 years of age)  Autumn to spring season  Sudden onset of a sore throat, headache, malaise, chills, anorexia, nausea and high fevers  Patients, especially young children, may experience vomiting, abdominal pain and seizures Scarlet Fever
  45. 45.  Eruption begins 12–48 hours later as blanchable erythema on the neck, chest and axillae  Subsequent generalization and development of tiny superimposed papules with sandpaper-like texture  Pastia’s lines (linear petechial streaks) are seen in the axillary, antecubital and inguinal areas  Cheeks are flushed with circumoral pallor
  46. 46. Strawberry tongue : initially white with bright red papillae, later becomes beefy red Throat is red and edematous, developing an exudate after 3–4 days; palatal petechiae and tender cervical adenopathy are often evident Desquamation occurs after 7–10 days, most prominently on the hands and feet and can last for 2–6 weeks.
  47. 47. sandpaper-like texture Pastia’s lines
  48. 48. Staphylococcal Scalded Skin Syndrome  Caused by exfoliative toxins ET-A and ET-B  Toxins target granular layer of epidermis, causing loss of adhesion and blistering  Young children (age ≤6 years) are most commonly affected  Prodrome of fever, malaise, and severally tender skin precedes the rash
  49. 49.  Erythema begins on the head and rapidly (hours) generalises  Skin becomes swollen, and fragile superficial vesicles and bullae form  Superficial desquamation/exfoliation occurs in 2 to 5 days, leaving denuded and crusted underlying skin
  50. 50. Toxic shock syndrome Caused by Staphylococcus aureus exotoxin (TSS-toxin-1) TSS is characterised by high fever (>39.6°C), hypotension (systolic BP <90 mmHg), pharyngitis, headache, GI symptoms, and a diffuse scarlatiniform rash Rash starts on the trunk and spreads centripetally. Extremities become oedematous, and the oral mucosa and tongue become hyperaemic Desquamation occurs 1 to 2 weeks after onset, starting on the palms and soles
  51. 51. • Clinical Criteria • An illness with the following clinical manifestations : • Fever ≥ 102.0°F • Rash: diffuse macular erythroderma • Desquamation: 1-2 weeks after onset of rash • Hypotension: SBP ≤ 90 mm Hg • Multisystem involvement (three or more of the following organ systems): (GI, Renal, Hepatic, Haematologic, CNS, Muscular & Mucous membrane) • Laboratory Criteria • Negative results on the following tests, if obtained : Blood or cerebrospinal fluid cultures (blood culture may be positive for Staphylococcus aureus) • Negative serologies for Rocky Mountain spotted fever, leptospirosis, or measles
  52. 52. Macular Erythema Conjuctival suffusion
  53. 53. Desquamation Of Palms
  54. 54. Post Transplantation : Acute GVHD Sudden onset of maculopapular exanthema occurs 1 to 3 weeks after transplant Can appear after blood product transfusion or solid organ transplant Occurs in 25% to 40% of HLA identical siblings and in 50% of non-HLA-identical transplants Predilection for acral areas (e.g. dorsal hands and feet, palms, soles, forearms, ears, as well as the upper trunk).
  55. 55. Pruritus is variable and a follicular pattern may be observed Severe cases : Diffuse erythroderma and desquamation, and mucous membranes (particularly conjunctiva) may be involved GI tract and liver involvement occur several days after cutaneous findings appear.
  56. 56. CLINICAL STAGING OF ACUTE GRAFT-VERSUS-HOST DISEASE Stage Skin Maculopapular Exanthem Liver (Bilirubin) Gut Diarrhea Grade Histologic Findings 1 <25% BSA 2 to <3 mg/dl 500–1000 ml/day, or persistent nausea I Focal vacuolar change of basal keratinocytes 2 25–50% BSA 3–6 mg/dl 1000–1500 ml/day II Grade 1 plus necrotic keratinocytes in the epidermis and/or hair follicle and dermal lymphocytic infiltrate 3 >50% BSA to generalized erythroderma 6–15 mg/dl >1500 ml/day III Grade 2 plus fusion of basilar vacuoles to form clefts and microvesicles 4 Generalized erythroderma with bulla formation >15 mg/d Severe abdominal pain with or without ileus IV Grade 3 plus large areas of separation of epidermis from dermis
  57. 57. Investigations
  58. 58. Drug Exanthem  Maculopapular Drug Rash  DRESS Syndrome TLC, DLC & Peripheral Blood Smear LFT/RFT  DRESS syndrome
  59. 59. Viral Exanthem  Haemogram with Peripheral Blood smear Serology • Viral Exanthem : IgM antibodies • Infectious Mononucleosis : Heterophile antibodies PCR & Culture
  60. 60. Bacterial Exanthem Platelet count LFT/RFT  Toxic shock syndrome ASO titre : Scarlet Fever PCR & Culture : Scarlet fever Meningococcaemia
  61. 61. Histopathology & Immunohistochemistry
  62. 62. Primary changes of maculopapular drug eruptions are -  Inter and intracellular edema as well as disruption of epidermal basal cells, showing pyknotic nuclei  Vacuolar alteration of basal keratinocytes with scattered individual dyskeratotic and necrotic keratinocytes Pathogenesis of drug-induced exanthems. Pichler W, Yawalkar N, Schmid S et al. Allergy. 2002 Oct;57(10):884-93.
  63. 63.  Interface dermatitis with superficial, mainly perivascular infiltrate of CD4 T-cells  CD4 and CD8 T-cells in equal number in DEJ zone and in epidermis  Some eosinophil is also found in dermis
  64. 64. Histologic features of most drug eruptions are not entirely specific Superficial infiltrates composed variably of L, N and Eo with or without interface changes suggest possibility of maculopapular drug exanthem Clinical correlation is very helpful to confirm diagnosis Cutaneous drug eruptions: a 5-year experience. Gerson D, Sriganeshan V, Alexis JB. J Am Acad Dermatol. 2008 Dec;59(6):995-9.
  65. 65. Epidermis of drug exanthem patients showed infiltration of CD4>CD8 cells Marked enhancement of perforin and granzyme B immunostaining Infiltration of cytotoxic T cells in drug-induced cutaneous eruptions. Yawalkar N, Egli F, Hari Y et al. Clin Exp Allergy. 2000 Jun;30(6):847-55.
  66. 66. Most common pattern of drug eruption is vacuolar interface dermatitis. Sparse P/V & interstitial infiltrate of N, Eo with subtle vacuolar changes at DEJ junction : virtually diagnostic of a drug eruption Viral exanthems can be associated with lymphocytic vasculitis – rare in drug eruption Some viral exanthem can be recognized by distinctive changes- Ballooning and multinucleated keratinocytes in measles Histopathology of drug eruptions - general criteria, common patterns, and differential diagnosis. Weyers W, Metze D. Dermatol Pract Concept. 2011 Jan 31;1(1):33-47.
  67. 67. Role of Immunohistology Soluble FAS ligand: a discriminating feature between drug-induced skin eruptions and viral exanthemas. Stur K, Karlhofer FM, Stingl G. J Invest Dermatol. 2007 Apr;127(4):802-7
  68. 68. Levels of sFASL in diseases of comparison groups Diseases Quantity sFASL (ng/ml) % Chickenpox 11 Negative 0 Shingles 11 Negative 0 Rubella 1 Negative 0 Fifth disease 1 Negative 0 Infectious mononucleosis 2 Negative 0
  69. 69. Based on FAS-ligand staining on tissue specimen Fas-ligand staining in non-drug- and drug-induced maculopapular rashes. Wang EC, Lee JS, Tan AW et al. J Cutan Pathol. 2011;38(2):196-201. DRUG Induced Maculopapular exanthem (n=10) Non DRUG induced Maculopapular exanthem (n=10) p Value FAS ligand staining 5 1 < 0.05 Tissue eosinophilia 6 (Moderate to dense) 2 (Moderate) 0.17
  70. 70. Maculopapular Drug Exanthem Maculopapular Viral Exanthem
  71. 71. Evidence for a role for IL-5 and eotaxin in activating and recruiting eosinophils in drug-induced cutaneous eruptions. Yawalkar N, Shrikhande M, Hari Y et al. J Allergy Clin Immunol. 2000 ;106(6):1171-6. Acute drug exanthem Normal subjects p Value IL-5 N < 0.05 Eotaxin N < 0.05
  72. 72. Staphylococcal Scalded Skin Syndrome
  73. 73. Acute GVHD
  74. 74. Algorithm to a patient with Maculopapular Exanthem
  75. 75. Maculopapular Rash Drugs Tender Rash with mucosal erosions Infectious Miscellaneous Non Infectious Inflammatory Cause Characteristic History & Clinical features With associated Systemic features & Eosinophilia Maculopapular drug Rash GVHD Dress Synd. Evolving into typical clinical manifestations SJS/TEN UnknownRickettsialViral Bacterial Clinical Suspicion Clinical Criteria 1. Familial Inf. syndromes 2. Still’s dsKawasaki ds Drug provocation HPE & IHC AEC CBC PBS LFT/RFT HPE HPE Serology HPE Serology Culture ASLO Serology Antigen detection Culture Acute-phase reactants CBC ECHO, ECG, Cardiac enzymes HPE H/o Transplant D ˂ 100 days Inv. Based on clinical suspicion of ds Laboratory Findings

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