Dermatology - Bright Red Rashes

From Iusmicm

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(An algorithm for diagnosing drug-induced cutaneous reactions)
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*Finally we exclude
*Finally we exclude
**If the dechallenge does not generate cessation or if the rechallenge does not cause the same reaction the we exclude drug-induced reactions from the ddx.
**If the dechallenge does not generate cessation or if the rechallenge does not cause the same reaction the we exclude drug-induced reactions from the ddx.
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Defining the spectrum •
 
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Polymyositis (no skin features)
 
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Dermatomyositis (skin + muscle) both adult and juvenile  Etiology
 
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Most are idiopathic … genetic susceptibility
 
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A very small subset are drug-induced  Pathogenesis
 
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Definite role of UV radiation in disease induction
 
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Complement membrane attack complex (MAC) has role
 
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Dermatomyositis Diagnostic Criteria
 
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Bohan & Peters criteria for diagnosis of dermatomyositis •
 
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Characteristic skin features
 
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Proximal muscle weakness  (usually painless)
 
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Muscle enzyme abnormalties  (CPK, aldolase)
 
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Characteristic EMG abnormalities
 
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Muscle biopsy    … currently MRI commonly used to dx muscle disease  **Each of these steps has some degree of limitation; in
 
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addition, do not need all 5 dx criteria to make diagnosis 
 
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Dermatomyositis – Clinical Features Heliotrope rash on upper eyelids
 
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Dermatomyositis – Clinical Features Photosensitivity, tendency towards poikiloderma, “spillover”
 
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What is “Poikiloderma” ?
 
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Hyperpigmentation Hypopigmentation Telangiectasias Atrophy  Most commonly seen with … Dermatomyositis UV radiation damage
 
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Ionizing radiation damage
 
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Dermatomyositis – Clinical Features Gottron’s papules, periungual telangiectasias
 
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Dermatomyositis – Clinical Features Gottron’s papules over IP joints, sparing between “knuckles”
 
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Diagnosis of Cutaneous Drug Reactions Background Information
 
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Key realities •
 
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Virtually any inflammatory cutaneous reaction pattern can be drug-induced at times
 
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Seldom does the clinical appearance alone point to a drug etiology (without aid of additional clinical information)  Higher risk
 
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drug reaction patterns can either cause …
 
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Fatal outcome (even if only remotely possible)
 
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Significant, irreversible morbidity 
 
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Diagnosis of Cutaneous Drug Reactions Higher Risk Drug Reaction Patterns
 
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Urticaria / Anaphylaxis  Erythema multiforme major  Stevens-Johnson syndrome  Toxic epidermal necrolysis  Morbilliform reactions
 
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with “hypersensitivity syndrome”  Vasculitis  … and the rest are relatively low risk (vast majority of rxn)
 
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Diagnosis of Cutaneous Drug Reactions An Algorithm
 
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Challenge •
 
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Timing of drug administration
 
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Literature reputation
 
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Personal experience  (… the least important component) Dechallenge
 
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Response to drug cessation
 
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Optional – not if essential drug; no help if rxn irreversible Rechallenge
 
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Gives highest level of certainty of algorithm steps
 
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Optional – not if higher risk pattern, not if alternative Rx Exclusion  (of non-drug causes of same pattern) 
 
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  It does not get any better than this …
 
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  Thank you for  your interest !!
 

Revision as of 12:20, 21 October 2011

Contents

Bright Red Rashes

  • There are five primary players in bright red rashes:
    • Urticaria
    • Erythema multiforme
    • Morbilliform eruptions
    • Lupus erythematosus
    • Dermatomyositis

General tendencies

  • In general, vascular reactions to insult can be described by color, topography, and time course:
    • Color: redness = erythema, results from excessive blood flow
    • Topography: raised lesions result from edmea
    • Time course: a reaction can be described as dynamic = evanescent
      • Note that evanescent means "soon passing out of sight or memory"
  • These three classic vascular reactions (erythema, edema, and evanescent) best describe urticaria, erythema multiforme, and morbilliform reactions

Urticaria

  • Urticaria is an allergic reaction that results in a bright red rash.
  • Urticaria is colloquially known as "hives"
    • The offending antigen is usually from a virus, a food, or a drug
    • Physical factors can also induce urticaria (think "SPACE"): sun exposure, pressure, aquagenic, cold, exercise
  • Pathogenesis of urticaria:
    • Induction of immune response results in a dilated (erythema), leaky (edema) vascular state that can be readily changed (evanescent)
    • Urticaria's EEE state is primarily driven by histamine acting on small dermal vessels
    • Purpura can result if immune complexes damage endothelium to the extent that RBCs escape into the tissue
      • Purpura generally lasts more than 24 hours at a single location
  • The rash of urticaria is often described as being annular.


  • back.gif
  • urticaria-1944.jpg
  • hives-urticaria-close-up-1651.jpg
  • 488.jpg

Erythema Multiforme

  • Erythema multiforme is an allergic reaction that results in a bright red rash.
    • Note that both urticaria and EM are allergic reactions.
  • Erythema multiforme is distinct from urticaria by its immune complexes and its apoptotic cytotoxic T cells.
  • Erythema multiforme is classified as minor and major based on how severe the manifestation.
    • EM minor is usually caused by herpes simplex virus, especially when EM is recurrent.
    • EM major is usually caused by drugs
  • EM Major has several named causes / syndromes: Stevens-Johnson syndrome and Toxic Epidermal Necrolysis
    • Both SJS and TEN are (usually) allergic reactions to drugs that result in necrolysis of keratinocytes of the lower epidermis.
    • Some consider TEN a more severe form or SJS.
  • EM presentation:


  • Stevens-Johnson Syndrome images:
    • SJS presents with widespread "targetoid" lesions
      • Note that these targetoid lesions are different than the target lesions in classical EM presentation
    • Stevens_Johnson-28.jpg
    • Picture%2023.png
    • Stevens_Johnson.JPG
    • edm565823.fig2.jpg
    • stevenjohnsons2.jpg
Target lesions versus Targetoid lesions
  • Target lesions:
    • Have concentric circles, especially when there are three concentric circles
    • Have central duskiness or a central blister
    • Have a relatively wide pale circle in between
    • Have an outer, thin, moderately erythematous circle
    • 0024_erythema_multiforme.JPG
    • target_lesions_of_erythema_multiforme.jpg
    • erythema-multiforme-minor.jpg
    • 2957_2979_1.JPG
    • 2957_2979_3.jpg
    • erthmul1.jpg


  • Targetoid lesions:
    • Suggest zonality but don't have 3 distinct concentric circles
    • 230px-EMminor09.JPG
    • ermulti1-s.jpg
    • 1.jpg


Morbilliform Reactions

  • Morbilliform reaction is through to be a T-cell mediated hypersensitivity to drugs or pathogens.
  • Etiology can be drugs or pathogens
    • Many different drugs (including antibiotics) can cause morbilliform reactions
    • Many pathogens can cause morbilliform reactions; usually enterovirus or group A streptococcus
  • One diagnosis the etiology by culturing the "company" kept by the rash
  • Morbilliform reaction manifests same symptoms regardless of causative agent
  • Morbilliform reaction is less evanescent than multifomre erythema and urticaria
  • Morbilliform reaction is characterized by truncal predominance
    • Recall that urticaria could show up anywhere and multiform erythema usually involved the oral mucosa and palms of the hands
  • Morbilliform is marked by its maculopapular rash
    • Recall that a macule is NOT raised but is discolored and that a papule IS raised but not necessarily discolored.
      • 804_f1.jpg
      • 774-2_default.jpg
Viral Exanthems
  • Most viral exanthems manifest as morbilliform reactions (except for varicella).
    • Recall that an exanthem is a skin eruption secondary to systemic disease.
    • Recall that varicella is a viral infection with herpes.
  • Recall the viral agents that cause the classic pediatric exanthems:
    • These all cause MORBILLIFORM reactions
    • Rubeola (Measles, paramyxovirus infection): cough, coryza, conjunctivitis, koplik spots
      • Rubeola is a systemic infection by paramyxovirus of the genus Morbillivirus
    • Rubella (German Measles, rubella virus infection): 3 day progression, progresses toward cephalocaudal poles
    • Roseola (Roseola Infantum, roseola virus infection): fever, followed with rash when "defervesce"
    • Mononucleosis: fever, fatigue, (f)pharyngitis, adenopathy, liver / spleen involvement
    • Fifth disease (Erythema infectiosum): slapped cheeks, fishnet erythema, recurrence
      • An example of "multiple stages" seen in many viral exanthems


  • Viral exanthums are characterized by: "dew drop on rose petal" formation, umbilicated vesicles, and multiple stages:
    • umbilicated-s.jpg
    • 37056-0550x0475.jpg
    • img0023.jpg

Lupus Erythematous

  • Lupus erythematous is an autoimmine disease
  • There are three types of lupus: systemic (SLE), discoid (DLE), and subacute cutaneous (SCLE)
    • Systemic and subacute cutaneous can be induced by drugs
  • All three types of SLE are considered idiopathic.
    • A genetic predisposition has been demonstrated.
  • SLE (systemic lupus erythematous) requires 4 of 11 ARA criteria be met.
  • DLE (discoid lupus erythematous) is primarily cutaneous in manifestation.
  • SCLE (subacute cutaneous lupus erythematous); subacute means it is not quite acute or chronic.
  • Pathogenesis of lupus eyrthmatous is though to be UV radiation induced and involves formation of immune complexes'.
Systemic lupus erythematous
  • Systemic lupus erythematous has 11 diagnostic criteria that can be divided into skin and mucus, systemic, and laboratory findings.
    • To diagnose SLE, you must "DUMP the SAC on the RAC"
  • Skin and mucosal criteria (DUMP):
    • Discoid lupus
    • Ulcers (oropharyngela, usually painless)
    • Malar rash
    • Photosensitivity
  • Systemic criteria (SAC):
    • Serositis (pleural, pericardial): inflammation of the serous tissues--things that line the lungs / heart (pleura, pericardium)
    • Arthritis
    • CNS (seizures, psychosis)
  • Laboratory criteria (RAC)
    • Renal dysfunction (Urinary analysis, elevated 24-hour urine protein levels)
    • Antinuclear antibodies (or others like anti-dsDNA or anti-Smith)
    • CBC (Hematology)
  • DUMP the SAC on the RAC (skin / mucosa, systemic, lab)


  • Systemic lupus erythematous presents with a malar rash and photosensitivity
    • There is sometimes "spillover" to unexposed sites, too, with the photosensitivity.
  • SLE can manifest scarring alopecia


Dermatomyositis

  • Dermatomyositis is an inflammation of the skin and muscle.
    • Note that polymyositis is simply the inflammation of the muscle with no skin features.
  • Like lupus erythematous, most dermatomyositis cases are idiopathic.
    • A small subset of dermatomyositis are drug-induced.
  • There is a definite role of UV radition in inducing dermatomyositis
  • Dermatomyositis is characterized by involvement of the complement systems membrane attack complex (MAC)


  • Diagnostic criteria for dermatomyositis:
    • Not all 5 are required
    • Skin features (to differentiate it from polymyositis)
    • Proximal muscle weakness which is usually painless
    • Muscle enzyme abnormalities (identified with CPK and aldolase levels)
      • CPK: creatine phosphokinase; adds kinase to creatinin; MM isoform in skeletal muscle, MB isoform in cardiac muscle, BB in smooth muscle
    • EMG abnormalities
    • Muscle biopsy
    • (currently we use MRI to dx, too)


  • Dermatomyositis presentation:
    • Heliotrope rash (upper eyelids)
    • Photosensitivity with spillover
    • Poikiloderma: see next section
    • Gottron's papules (area between knuckles is spared)
    • Periungual telangiectasias


  • Heliotrope rash (upper eyelids):
    • heliotrope%20rash.jpg
    • heliotrope%20rash%20II.jpg
    • Heliotrope.jpg
  • Photosensitivity with spillover:
    • photosensitivity17.jpg
    • gem_04_img0508.jpg
    • photosensitivity.jpg
  • Poikiloderma: see next section
  • Gottron's papules (area between knuckles is spared):
    • 0307ConPERheum2B.jpg
    • Dermatomyositis_Gottrons_papules_1_low.jpg
    • 1866.jpg
    • symptom_gottron1.jpg
    • fig13.jpg
  • Periungual telangiectasias:
    • Dermatomyositis6.jpg
    • md_99-06-0061.tif.jpg
    • 56.jpg
Poikiloderma
  • Poikiloderma is characterized by hyperpigmentation, hypopigmentation, telangiectasias, and / or atrophy.
  • Poikiloderma is seen in conjunction with dermatomyositis, UV radiation damage, and ionizing radiation damage.
  • poikilodermaofCivatte_11790_lg.jpg
  • poikiloderma.jpg
  • Poikiloderma_1_low.jpg
  • Poikiloderma-After.jpg
  • 2266_poikiloderma_of_civatte.jpg
  • vbmBA2lrg.jpg
  • large_poikiloderma_sun_damage.jpg
  • 3-49-4.jpg
  • sn22_poikiloderma.jpg
  • ipl7.jpg


Drug reactions

  • Drug reactions can generate every possible different cutaneous pattern
  • Rarely does clinical presentation afford enough information to dx drug-induced reaction
    • Usually requires additional information like lab values
  • Some patterns caused by drug reactions are considered higher risk
    • These patterns have significant morbidity or have mortality associated with them
    • High risk patterns include: urticaria / anaphylaxis, erythema multiforme major (SJS, TEN), morbilliform reactions (with hypersensitive syndrome characteristics), and vasculitis
  • All the rest of the patterns are relatively low risk for morbidity and mortality.


An algorithm for diagnosing drug-induced cutaneous reactions
  • The process is, in general, a series of controlled challenges to the pt with the drug: challenge, dechallenge, rechallenge, exlusion
  • First we challenge with the drug
    • An important aspect to the challenge is the time of drug administration
    • This should be informed by the literature and one's own experience with the drug
  • Then we "dechallenge"
    • We watch for cessation of the drug reaction
    • Dechallenging is options, unless the drug is essential for the pt's life
    • Dechallenging will not result in cessation of recation if the reaction is irreversible
  • Next we rechallenge
    • This repetition gives the highest level of certainty that the reaction is drug-induced
    • Rechallenging is optional
      • Rechallenge is not an option if the challenge resulted in a higher-risk reaction pattern (which would advise no rechallenge for safety reasons)
      • Rechallenge is not an options if there is an alternative therapy to the drug that causes a reaction (because we shouldn't give a drug we know causes an adverse reaction is there is still another potentially non-reactive drug available)
  • Finally we exclude
    • If the dechallenge does not generate cessation or if the rechallenge does not cause the same reaction the we exclude drug-induced reactions from the ddx.
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