Dermatology - Bright Red Rashes

From Iusmicm

Contents 1 Bright Red Rashes 1.1 General tendencies 1.2 Urticaria 1.3 Erythema Multiforme 1.3.1 Target lesions versus Targetoid lesions 1.4 Morbilliform Reactions 1.4.1 Viral Exanthems 1.5 Lupus Erythematous 1.5.1 Systemic lupus erythematous 1.6 Dermatomyositis 1.6.1 Poikiloderma 1.7 Drug reactions 1.7.1 An algorithm for diagnosing drug-induced cutaneous reactions

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.

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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:
  • Target lesions on palsm
  • Oral mucosal involvement
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• 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
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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
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• Targetoid lesions:
  • Suggest zonality but don't have 3 distinct concentric circles
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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.
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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:
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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):
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• Photosensitivity with spillover:
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• Poikiloderma: see next section
• Gottron's papules (area between knuckles is spared):
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• Periungual telangiectasias:
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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.
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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.

Defining the spectrum • Polymyositis (no skin features)

• Dermatomyositis (skin + muscle) both adult and juvenile Etiology

• Most are idiopathic … genetic susceptibility

• A very small subset are drug-induced Pathogenesis

• Definite role of UV radiation in disease induction

• Complement membrane attack complex (MAC) has role

Dermatomyositis Diagnostic Criteria Bohan & Peters criteria for diagnosis of dermatomyositis • Characteristic skin features

• Proximal muscle weakness (usually painless)

• Muscle enzyme abnormalties (CPK, aldolase)

• Characteristic EMG abnormalities

• Muscle biopsy … currently MRI commonly used to dx muscle disease **Each of these steps has some degree of limitation; in

addition, do not need all 5 dx criteria to make diagnosis

Dermatomyositis – Clinical Features Heliotrope rash on upper eyelids 12

Dermatomyositis – Clinical Features Photosensitivity, tendency towards poikiloderma, “spillover” 13

What is “Poikiloderma” ? Hyperpigmentation Hypopigmentation Telangiectasias Atrophy Most commonly seen with … Dermatomyositis UV radiation damage

Ionizing radiation damage

Dermatomyositis – Clinical Features Gottron’s papules, periungual telangiectasias 14

Dermatomyositis – Clinical Features Gottron’s papules over IP joints, sparing between “knuckles” 15

Diagnosis of Cutaneous Drug Reactions Background Information Key realities • Virtually any inflammatory cutaneous reaction pattern can be drug-induced at times

• Seldom does the clinical appearance alone point to a drug etiology (without aid of additional clinical information) Higher risk

drug reaction patterns can either cause …

• Fatal outcome (even if only remotely possible)

• Significant, irreversible morbidity

Diagnosis of Cutaneous Drug Reactions Higher Risk Drug Reaction Patterns Urticaria / Anaphylaxis Erythema multiforme major Stevens-Johnson syndrome Toxic epidermal necrolysis Morbilliform reactions

with “hypersensitivity syndrome” Vasculitis … and the rest are relatively low risk (vast majority of rxn)

Diagnosis of Cutaneous Drug Reactions An Algorithm Challenge • Timing of drug administration

• Literature reputation

• Personal experience (… the least important component) Dechallenge

• Response to drug cessation

• Optional – not if essential drug; no help if rxn irreversible Rechallenge

• Gives highest level of certainty of algorithm steps

• Optional – not if higher risk pattern, not if alternative Rx Exclusion (of non-drug causes of same pattern)

 It does not get any better than this … 

  Thank you for  your interest !!