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191 Approach to the  Adult RashHeather Murphy-Lavoie and Tracy Leigh LeGros

PATHOPHYSIOLOGY

A rash is a skin eruption that has a defined morphology and location. The morphology of the rash is usually distinct and related to the pathophysiologic dysfunction of the skin. Most severe rashes begin as exanthems (from the Greek exanthema, which means “breaking out,” and anthos, which means “flow-ering”). These rashes subsequently take on a particular mor-phology, characteristic lesions, or distribution. Table 191.1 delineates the most common terms used for skin lesions. Understanding these terms helps one better document pro-gression of disease and facilitates communication with con-sulting physicians.

PRESENTING SIGNS AND SYMPTOMS

Eliciting the initial distribution and progression of a rash is essential. Additionally, the involvement of palms, soles, and mucous membrane is of key importance. It should be kept in mind that dysphasia, as well as eye or genital irritation, may be a manifestation of as mucosal involvement and is often the initial symptom of several life-threatening conditions. The rash’s rapidity of progression is also an essential in diagnosis. Box 191.1 categorizes these important findings.

PHYSICAL EXAMINATION TIPSEvaluation of vital signs is essential. Fever and hypotension, in particular, are ominous findings that mandate expedited and intensive care. Additional findings of concern on physical examination include a new-onset heart murmur or nuchal rigidity. Generalized lymphadenopathy is present with many illnesses, including mononucleosis, human immunodeficiency virus (HIV) infection, other infections, serum sickness, and drug reactions.

To ensure that lesions on the back, buttocks, and perineum are identified, patients should be completely undressed. Patients are often unaware of lesions present in these loca-tions. Shoes and socks should also be removed, especially in diabetic patients. Toenails should be inspected closely for signs of systemic disease or fungal infection. Some fungal foot infections can cause an id (autoeczematization) reaction and exacerbate eczema in the upper extremities. Treatment of the fungal infection will be necessary to control the dermati-tis. Additionally, the fingers, toes, palms, and soles should be examined closely for the distribution of the rash and stigmata of endocarditis.

• Rashesareacommonreasonforavisittotheemergencydepartment.Somerashesaresimpleandstraightforward.However,othersrepresenttheinitialcomplaintofapatientwithalife-threateningdisease.

• Feverwitharashiskeytorecognizingsomeofthemoredangerousconditions.

• ThekeyfordifferentiatingadiffuselyerythematousrashincludesthepresenceorabsenceoftheNikolskysign.

• Keyfactorsfordifferentiatingamaculopapularrashincludeitsdistributionandtargetlesions.

• Avesiculobullousrashisalsodifferentiatedbydistribution;alocalizedordiffusedistributionhelpsnarrowthedifferentialdiagnosis.

• Petechial/purpuricrashesaredifferentiatedbythepresenceorabsenceofpalpablelesions.

• Petechiaedonotblanchwithpressure.• Palpablepurpuraoccursinvasculiticdiseases

secondarytoinflammationorinfection.• Nonpalpablepurpuraischaracteristicof

thrombocytopenicconditions.• Bullousrashwithmucosalinvolvementisworrisome,

andsteroidtherapymaybewarranted.• Acarefulhistoryandphysicalexaminationarecrucial

fornarrowingthedifferentialdiagnosisofanunknownrash.

KEY POINTS

EPIDEMIOLOGY

Evaluation of rashes ranks highly among the top 20 reasons for visits to the emergency department.

A well-reasoned algorithmic approach to the evaluation of rashes might aid the emergency medicine specialist in identi-fying the most common and potentially lethal rash syndromes. Although an exhaustive review of all potential fungal, para-sitic, and viral causes of rash is beyond the scope of this chapter, the algorithms presented will equip physicians to quickly recognize the most common and critical rashes. Pedi-atric rashes are discussed in detail in Chapter 18. Additionally, the most life-threatening rashes are discussed in more detail in Chapter 192.

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SPECIFIC SIGNSTwo signs are important in the evaluation of these rashes: the Nikolsky sign and the Asboe-Hansen sign. A positive Nikol-sky sign (Fig. 191.1) is noted when slight rubbing of the skin results in exfoliation of the outermost layer with lateral exten-sion of the erosion into the intact skin. The area of denuded skin is pink and tender. The Asboe-Hansen sign (indirect Nikolsky sign or Nikolsky II sign) is extension of a blister into normal skin with the application of light pressure on the top of the blister. All patients with tender, blistering, or slough-ing skin should be evaluated serially for these important signs.

DIFFERENTIAL DIAGNOSES AND MEDICAL DECISION MAKING

History taking is an essential component in formulating appropriate differential diagnoses and guiding medical decision making. Inquiry regarding the patient’s travel, medical, occupational, recreational, and medicinal history is required. Once the history and physical examination are com-plete, in-depth evaluation of the rash is in order. The differ-ential diagnoses can be narrowed by categorizing the rash as erythematous, maculopapular, petechial/purpuric, or vesiculobullous.

TRAVEL HISTORYLyme disease is common in the mid-Atlantic, central, western, and northeastern parts of the United States. Patients who have recently traveled to the Caribbean may have dengue fever. In addition, patients reporting recent camping and travel through

Fig. 191.1 Fragileblistersruptureeasilytoformpainfulerosions.Fingerpressureseparatesnormal-appearingepidermisandproducesanerosion(Nikolskysign).Pressureontheedgeofablisterspreadstheblisterintounaffectedskin(Asboe-ltansensign).(FromHabifTP,editor.Clinicaldermatology,5thed.Philadelphia:Mosby;2009.Figure16-14.)

BOX 191.1 Distribution and Progression of a Rash

Distribution and SpreadBeginperipherally,thenspreadcentrally

– RockyMountainspottedfever– Erythemamultiforme– Vasculitides

Begincentrally,thenspreadperipherally– Viralexanthems– Smallpox

Involvement of Palms and SolesDiffuseinvolvement(moreseriousandlethal)

– RockyMountainspottedfever– Erythemamultiforme– Stevens-Johnsonsyndrome– Toxicepidermalnecrolysis– Syphilis– Bacteremicendocarditis

Localizedinvolvement– Contactdermatitis– Infectiousprocess

Involvement of Mucous MembranesToxicepidermalnecrolysisStevens-JohnsonsyndromePemphigusvulgarisKawasakidiseaseViralsyndromes

Rapidity of Rash ProgressionSpreadinminutes

– UrticarialanaphylaxisSpreadinhours

– MeningococcemiaSpreadindays

– Drugreactions

Table 191.1 Common Terms for Skin Lesions

TERM DESCRIPTION

Lesion Singlesmalldiseasedarea

Macule Circumscribedareaofchangewithoutelevation

Rash Skineruptionthatismoreextensivethanasinglelesion

Papule Solidraisedlesion<1cm

Nodule Solidraisedlesion>1cm

Plaque Raisedconfluenceofpapules>1cm

Pustule Fluid-filledareacontainingpurulence

Vesicle Fluid-filledarea<1cmcontainingclearfluid

Bullae Fluid-filledarea>1cm

Petechiae Pinpointflatroundspots<3mmcausedbyintradermalbleedingthatdonotblanch

Purpura Hemorrhagicarea>3mmthatdoesnotblanch

Exanthem Rashoutsidethebody(skin)

Enanthem Rashinsidethebody(mucousmembranes)

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disease, and scarlet fever. Refer to Chapter 192 for review of TEN, TSS, and erythroderma.

Maculopapular RashesThe term maculopapule is a portmanteau of macule and papule. Maculopapular rashes are differentiated by the distri-bution of the rash and systemic toxicity (Fig. 191.3). Patients with centrally distributed rashes who appear toxic and febrile have a wide differential diagnosis; however, it is paramount that patients living in endemic areas be assessed for Lyme disease. Those with centrally distributed rashes but no signs of toxicity usually have either a drug reaction or pityriasis rosea. Patients with peripherally distributed rashes have a broader differential diagnosis that is dependent on systemic toxicity, the presence or absence of target lesions, and whether the rash is located on the flexor or extensor surfaces. Target lesions (Fig. 191.4) are pathognomonic for SJS or erythema multiforme (EM). The target lesion of Lyme disease is usually a single large bull’s eye that measures at least 5 cm in diameter (erythema migrans). Patients with peripheral lesions and sys-temic toxicity but without target lesions require emergency evaluation for meningococcemia, RMSF, and syphilis. Non-toxic patients with a peripherally distributed rash and no target lesions require further assessment for flexor involvement (scabies or eczema) or extensor involvement (psoriasis). Please refer to Table 191.2 for review of EM minor and major. See Chapter 18 for review of viral exanthems. Please refer to Chapter 192 for review of Lyme disease, meningococcemia, RMSF, SJS, and syphilis.

Petechial/Purpuric RashesThese rashes can be especially challenging and are associated with devastating differential diagnoses; however, an algorith-mic approach can help the physician narrow the diagnosis with confidence (Fig. 191.5). By definition, petechiae do not blanche with pressure; additionally, remembering the cause of palpable versus nonpalpable lesions is paramount. Palpable (raised) purpura occurs in vasculitic diseases secondary to inflammation or infection. Nonpalpable purpura (flat, sub-cutaneous hemorrhages) are seen with thrombocytopenic conditions. Patients with petechial/purpuric rashes and fever or toxicity require emergency evaluation. If the lesions are

wooded areas are candidates for Rocky Mountain spotted fever (RMSF) and other tick-borne illnesses.

MEDICAL, OCCUPATIONAL,  AND RECREATIONAL HISTORYPatients with diabetes, HIV infection, or a history of intrave-nous drug abuse and patients undergoing chemotherapy are at risk for diseases associated with high morbidity and mortality (meningococcemia, thrombotic thrombocytopenic purpura [TTP], necrotizing fasciitis, disseminated zoster, Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis [TEN], and sepsis). Persons with valvular heart disease are at increased risk for endocarditis. College students, military personnel, and employees of daycare facilities are more likely to contract meningococcemia. Hunters and campers are at risk for tick-borne illnesses.

MEDICINAL HISTORYPotentially lethal drug reactions such as SJS, TEN, anaphy-laxis, and angioedema mandate specific and emergency inter-ventions, but discontinuing the offending agent is the initial step. This will reduce the risk for death by 30% daily! Addi-tionally, many patients self-treat rashes before seeking medical care. Steroid creams, in particular, may significantly alter the morphology of the rash. It is important to note any treatments before initial evaluation.

THE ALGORITHMIC APPROACHErythematous RashesThese rashes are characterized by diffuse redness of the skin as a result of capillary congestion. Erythematous rashes are differentiated by the presence or absence of fever and the Nikolsky sign (Fig. 191.2).1 If a Nikolsky sign is present, the diagnosis is narrowed substantially, usually to TEN in adults and to staphylococcal scalded skin syndrome (SSSS), gener-ally in infants and young children. If fever is present without a Nikolsky sign, the differential diagnosis includes Kawasaki disease, scarlet fever, erythroderma, and toxic shock syn-drome (TSS). Patients with an erythematous rash but without a fever or Nikolsky sign may be having an anaphylactic reac-tion or a reaction to vancomycin, scombroid, or alcohol expo-sure. Please refer to Chapter 18 for review of SSSS, Kawasaki

Fig. 191.2 Algorithm for erythematous rashes.SSS,Scaldedskinsyndrome;TEN,toxicepidermalnecrolysis(FromMurphy-LavoieH,LeGrosTL.Emergentdiagnosisoftheunknownrash:analgorithmicapproach.EmergMed2010;42[3]:6-17.)

Erythematous rash

Nikolsky sign

Yes No

FebrileStaph SSS (child)

TEN (adult)

AfebrileTEN (adult)

FebrileToxic shock syndrome (TSS)

(mucous membranes)Erythroderma

Kawasaki syndrome (children)Scarlet fever (sandpaper)

AfebrileAnaphylaxisScrombroidAlcohol flush

Vancomycin redman syndrome

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Fig. 191.3 Algorithm for maculopapular rashes.(FromMurphy-LavoieH,LeGrosTL.Emergentdiagnosisoftheunknownrash:analgorithmicapproach.EmergMed2010;42[3]:6-17.)

Maculopapular rash

Centraldistribution

Peripheraldistribution

Fever/ill?

Yes No

Fever/ill?

Viralexanthem

Drug reactionPityriasis

(herald patch)

Target Lesiondistribution

Flexor ExtensorStevens-JohnsonErythema multiforme

Lyme disease

MeningococcemiaRocky Mountain

spotted feverSyphilis Scabies

EczemaPsoriasis

Yes No

Yes No

palpable, the differential diagnosis includes meningococce-mia, disseminated gonococcal disease, endocarditis, RMSF, and Henoch-Schönlein purpura (HSP). Those with petechial/purpuric rashes and fever or toxicity but without palpable lesions may have purpura fulminans, disseminated intravas-cular coagulopathy (DIC), or TTP. If the patient is afebrile and has a petechial or purpuric rash, the diagnosis may be far simpler and less ominous. Nontoxic patients with palpable lesions may have a vasculitis; those with nonpalpable lesions may have idiopathic thrombocytopenic purpura (ITP). A detailed history may elucidate the cause of a vasculitis by identifying a key drug use history, recent illness, or an under-lying symptom characteristic of the triggering disease.5 In patients with ITP, it is important to exclude other causes of thrombocytopenia, including HIV infection, hepatitis, auto-immune disease, liver or renal disease, cancer, infection, preg-nancy, alcohol use, and exposure to heparin or other inciting drugs or agents. Patient with ITP also require a full assess-ment of their risk for complications because of their throm-bocytopenic condition, including age older than 60 years, engagement in athletic sport activities, peptic ulcer disease, menorrhagia, and intracranial hemorrhage.4 Please refer to Table 191.3 for review of disseminated gonococcemia, sec-ondary vasculitis, and ITP. Box 191.2 lists a vasculitis clas-sification scheme, and these conditions are discussed in more detail in Chapter 110. Please refer to Chapter 18 for review of HSP and Chapter 192 for review of meningococcemia, endocarditis, RMSF, TTP, and purpura fulminans/DIC.

Vesiculobullous RashesVesiculobullous rashes provoke significant angst in many phy-sicians (Fig. 191.6). However, the differential diagnosis can

be greatly simplified by categorizing patients with these rashes as febrile or afebrile and noting whether the distribu-tion of the rash is diffuse or localized. Patients with a diffuse vesiculobullous rash and a fever may have varicella or a more devastating illness such as smallpox, disseminated gonococcal disease, or purpura fulminans/DIC. Necrotizing fasciitis and hand-foot-and-mouth disease are characterized by localized lesions and fever. In afebrile patients with a diffuse vesicu-lobullous rash, the differential diagnosis includes bullous pemphigus (BP) and pemphigus vulgaris (PV). One of the distinguishing features is based on the Nikolsky sign. A posi-tive Nikolsky sign is seen with PV but is absent in BP. These

BOX 191.2 Vasculitis Classifications

Large Vessel VasculitisTemporalarteritisTakayasuarteritis

Medium Vessel VasculitisPolyarteritisnodosaKawasakidisease

Small Vessel VasculitisWegenergranulomatosisChurg-StrausssyndromeMicroscopicpolyangiitisHenoch-SchönleinpurpuraEssentialcryoglobulinemicvasculitisCutaneousleukocytoclasticvasculitis

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Fig. 191.4 Targetlesionsonthepalmsandsolesarehighlycharacteristicoferythemamultiforme.Lesionsbeginasdullredmaculeswithavesicledevelopinginthecenter.Theperipherybecomescyanotic.(FromHabifTP,editor.Clinicaldermatology,5thed.Philadelphia:Mosby;2009.Figure18-4.)

A

B

C

Fig. 191.5 Algorithm for petechial/purpuric rashes.GC,Gonococcaldisease;HSP,Henoch-Schönleinpurpura;ITP,idiopathicthrombocytopenicpurpura;RMSF,RockyMountainspottedfever;TTP,thromboticthrombocytopenicpurpura.(FromMurphy-LavoieH,LeGrosTL.Emergentdiagnosisoftheunknownrash:analgorithmicapproach.EmergMed2010;42[3]:6-17.)

Petechial/purpuric rash

Febrile Afebrile

PalpableMeningococcemiaDisseminated GC

EndocarditisRMSFHSP

Not palpablePurpurpa

fulminans/DICTTP

PalpableVasculitis

Not palpableITP

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Table 191.2 Erythema Multiforme

Causes PossiblyautoimmuneUnknownin50%

Exposures Infections:herpessimplex,Mycoplasma,fungiDrugexposures:sulfaandotherantibiotics,anticonvulsants

Classification Erythemamultiformeminor Erythemamultiformemajor

Description Mild,self-limitedrash Severe,life-threateningdiseasewithsignificantmucousmembraneinvolvement2

Prodromalsymptoms

Noprodromalsymptoms MildupperrespiratoryinfectionwithmoderatefeverCough,sorethroat,chestpainVomitinganddiarrheaRashappearsin1-2wk

Rashcharacteristics

Symmetricextremitylesionsthatdevelopintotargetlesions

Beginsasamaculopapularrashthatevolvesintotargetlesions;rapidlyprogressivewithcentripetalspread

Distribution Lowerextremities Palms,soles,dorsaofhands,face,andextensorsurfaces

Mucousmembraneinvolvement

None SignificantmucousmembraneinvolvementEyeinvolvement(10%);oftenbilateral,purulentconjunctivitis

Pruritic Yes No

Diagnosis Confirmedwithbiopsy Confirmedwithbiopsy

Treatment UsuallyoutpatientmanagementSymptomaticsupportAnalgesicsColdcompressesTopicalsteroidsTreatmentofthecauseDiscontinueuseoftheoffending

agentDermatologyfollow-up

UsuallyinpatientmanagementTreatmentofthecauseDiscontinueuseoftheoffendingagentFluidandelectrolytebalanceAnalgesicsWoundcare(avoidsilversulfadiazine)Soothingoralsolutions3

Dermatologyconsultation3

Ophthalmologicconsultation3

Intravenoussteroidsmayincreasecomplications

Physicalexaminationpearl

IncontrasttoStevens-Johnsonsyndromeortoxicepidermalnecrolysis,thetargetlesionsoferythemamultiformearediscreteratherthanconfluent,andtheskinisnotusuallytender.Theskinisverytenderwithtoxicepidermalnecrolysis

Fig. 191.6 Algorithm for vesiculobullous rashes.DIC,Disseminatedintravascularcoagulopathy;GC,gonococcaldisease.(FromMurphy-LavoieH,LeGrosTL.Emergentdiagnosisoftheunknownrash:analgorithmicapproach.EmergMed2010;42[3]:6-17.)

Vesiculobullous rash

Febrile Afebrile

Diffusedistribution

Varicella/chickenpoxSmallpox

Disseminated GCPurpurpa fulminans/DIC

Localizeddistribution

Necrotizing fasciitisHand-foot-and-mouth

disease

Diffusedistribution

Nikolskysign

Localizeddistribution

Contact dermatitisHerpes zoster

Dyshidrotic eczemaBurns

(+) Nikolsky signPemphigus vulgaris

(–) Nikolsky signBullous pemphigus

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Table 191.3 Selected Petechial/Purpuric Rashes

DISSEMINATED GONOCOCCEMIA SECONDARY VASCULITIS

IDIOPATHIC THROMBOCYTOPENIC PURPURA

Causes Neisseria gonorrhoeaeMorefrequentin

womenAssociatedwith

menses

InfectionorinflammationMalignancyCollagenvasculardiseaseSarcoidDrugreactions5,6

Antibiotics,analgesicsUrticariaCryoglobulinemiaTransplantation

Isolatedthrombocytopenia(peripheraldestruction)asaresultofIgGantibodiesagainstplateletmembraneproteins4

Precedinginfectioncommon

Signsandsymptoms

PetechialrashFeverConstitutional

symptoms7

ArthralgiasMaybemigratoryTwothirdsare

polyarthralgiasTenosynovitis

Rash(usuallyasymptomatic)Nonthrombogenicpalpablepurpuric

cropsonlowerextremitiesandbuttocks(88%)5

Necroticorcrustedulcers5

Nonspecificsymptoms5

Fever,jointpainDiarrhea,abdominalpainPruritus

BleedingdiathesisBruisingHemorrhagicbullaeonmucous

membranesEpistaxisMenorrhagia

MoreacutemanifestationinchildrenMorechronicmanifestationinadults

Work-up CulturesBloodCervical,penileThroat

GramstainSexuallytransmitted

diseasescreens

DetailedhistorySkinbiopsyDirectimmunofluorescence

ExcludeotherthrombocytopeniasAssessincreaseinbleedingrisk7

Treatment Ceftriaxoneintravenously

Ciprofloxacinforcephalosporin-allergicpatients

NontoxicpatientsDischargeClosefollow-up

AdmissionforillpatientsHypertensionPulmonaryhemorrhageEnd-organdamageChangesinmentalstatusIllappearance

HospitaladmissionHigh-doseintravenousglucocorticoidsIntravenousimmunoglobulinPlateletsforseverehemorrhage(immediately

afterintravenousimmunoglobulin)EmergencyhematologyconsultationBonemarrowevaluation

Patient>60yrConsiderationofsplenectomyfor

persistentthrombocytopenia8

entities are regularly confused, and it is essential to differenti-ate them urgently. It is important to remember that both BP and PV have strong associations and known triggers. For those with BP, the list of drug triggers includes furosemide, ibupro-fen, captopril (or other thiol-containing compounds), penicil-lamine, and antibiotics. Patients with PV have similar drug triggers (with the addition of rifampin). Please refer to Table 191.4 for additional associations for PV and BP. The differ-ential diagnosis is simpler and less of an emergency in a patient who is afebrile with a localized vesiculobullous rash; contact dermatitis, herpes zoster, dyshidrotic eczema, and burns are included in the differential diagnosis. Please refer to Table 191.4 for a discussion of PV and BP. Refer to Chap-ters 18 and 192 for review of varicella and Chapter 192 for review of smallpox, purpura fulminans/DIC, and necrotizing fasciitis.

TREATMENT

The type of rash, the overall health and physical reserves of the patient, and the rapidity of diagnosis determine treatment.

Many of these diseases are associated with significant morbid-ity and mortality, and a high index of suspicion is required to prevent a delay in diagnosis.

ERYTHEMATOUS RASHESFebrile Patients with a Positive Nikolsky SignThese patients are systemically ill and require intensive treat-ment. Patients with SSSS usually require hospitalization for fluid and electrolyte management and supportive wound and skin care. Young, well-appearing patients with SSSS and minimal skin sloughing may be managed as outpatients. However, adult patients with SSSS have a 60% mortality rate and require much closer monitoring. Antibiotics are usually recommended, but is it unclear whether they measurably alter the course of the disease. Please refer to Chapters 18 and 192 for further review. Patients with TEN require immediate dis-continuation of the offending agent, wound care, eye care, fluid and electrolyte resuscitation, and admission to either an intensive care unit (ICU) or burn unit. Intravenous immune globulin (IVIG) may be helpful, but it has yet to be approved by the Food and Drug Administration for this use. Most

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Afebrile Patients Without a Nikolsky SignThese patients have exposure reactions. Anaphylaxis is a medical emergency that calls for immediate intervention. These patients require intravenous access, cardiac monitoring, high-flow oxygen, fluid resuscitation, airway management as indicated (laryngeal edema), inhaled β-agonists (wheezing or stridor), corticosteroids or aminophylline (for refractory bron-chospasm), and epinephrine. The use of epinephrine is not contraindicated in this emergency. However, there is a death correlation associated with delay in administration. Scom-broid toxicity is treated with antihistamines and supportive care. Complications are rare, and usually no further treatment is needed. Patients who experience an alcohol flush reaction require supportive care and should limit their alcohol con-sumption because their symptoms are due to an accumulation of acetaldehyde, a known carcinogen. Vancomycin red man syndrome is a drug-induced infusion reaction characterized by flushing and an erythematous rash secondary to mast cell degranulation. Hypotension and angioedema may occur and require close monitoring. Treatment consists of antihista-mines. An extreme vancomycin-induced drug reaction results in an overwhelming exfoliative dermatitis that requires hospital admission, fluid and electrolyte management, skin

physicians recommend against steroid use. It is important to avoid sulfadiazine on these wounds because sulfa is a common offending agent.

Febrile Patients Without a Positive Nikolsky SignThese patients are systemically ill and require intensive treatment. Patients with TSS require immediate removal of the infective material, intravenous antibiotics, fluid resus-citation, ICU admission, and consideration of the use of IVIG. Erythroderma is a devastating and overwhelming disease. All patients require admission, fluid and electrolyte monitoring, skin care, antihistamines, prevention of second-ary infection, treatment of the underlying cause, and topical steroids. Systemic steroids are controversial. Recovery is long and recurrences are common. Patients with Kawasaki syndrome require high-dose aspirin immediately, hospi-talization, and IVIG. Those with scarlet fever require peni-cillin to prevent local suppurative complications and acute rheumatic fever. Please refer to Chapter 18 for review of scarlet fever. Refer to Chapter 192 for review of erythro-derma. Refer to Chapters 18 and 192 for review of Kawasaki disease and TSS.

Table 191.4 Pemphigus Vulgaris and Bullous Pemphigus

PEMPHIGUS VULGARIS BULLOUS PEMPHIGUS

Causes Generalizedmucocutaneousautoimmuneblistering

Chronic,cutaneous,autoimmuneblistering

Characteristics Patients50-60yroldInitialmucosalinvolvement(60%)Progressiontononpruriticskinblisters9

PossibleskinsloughingNikolskyandAsboe-Hansensigns

Olderpatients(averageage,65yr)InfantincidencerisingInitialmucosalinvolvement(10-25%)9

Rashisgeneralizedandbullous

Associations AutoimmunediseaseMyastheniagravisThymoma

Triggers(drugs,emotionalstress)

TriggersLichenplanus/psoriasisUltravioletradiation,x-raytherapyChildhoodvaccinesDrugs

Clinicalsign PositiveNikolskysign NegativeNikolskysign

Diagnosis ClinicalfindingsSkinbiopsy

ClinicalfindingsHistopathologicevaluationofblisteredges

Treatment HospitaladmissionFluidandelectrolytebalancePaincontrolInfectionmonitoringImmunosuppressantdrugs9,10

SupportivecareOralortopicalsteroidsTetracyclineImmunosuppressiveagentsDapsoneDermatologyconsultationOtolaryngologicconsultation(mucosalinvolvement)Ophthalmologicconsultation(ocularinvolvement)10

Prognosis Generallypoor50%mortality(beforesteroids)10-20%withsteroids3

BetterprognosisLessoralinvolvementMaypersistforyears(waxingandwaning)Maybefatalinfrailpatients

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Refer to Chapter 192 for further information on meningococ-cemia, RMSF, and syphilis.

Peripheral, Flexural, Maculopapular Rashes in Well-Appearing PatientsThese patients may have scabies or eczema. Scabies usually responds to household hygiene, a scabicide, and antihista-mines. Eczema (Fig. 191.7) is treated with topical steroids, cold compresses, and ultraviolet light.

Peripheral, Extensural, Maculopapular Rashes in Well-Appearing PatientsThese patients may have psoriasis and usually respond well to the use of moisturizers, salicylic acid, light therapy, sun exposure, topical steroids, oatmeal baths, stress reduction, and dermatologic follow-up.

PETECHIAL/PURPURIC RASHESPalpable Petechial/Purpuric Rashes in Febrile PatientsThese patients have wide differential diagnoses with high morbidity and mortality. Meningococcemia and RMSF were discussed in the section related to the treatment of maculo-papular rashes. Treatment of disseminated gonococcemia is reviewed in Table 191.3. Patients with endocarditis require early recognition, intensive therapy, broad-spectrum anti-biotics to cover methicillin-resistant Staphylococcus (with subsequent guidance by blood cultures), and cardiology con-sultation. See Chapter 192 for further information on endo-carditis. HSP is a small vessel vasculitis that is usually self-limited, and treatment is supportive. NSAIDs are used to reduce joint and soft tissue pain. Patients with significant bleeding, intussusception, and renal failure require admission for HSP. Please refer to Chapter 192 for review of endocar-ditis and Chapter 18 for review of HSP.

Nonpalpable Petechial/Purpuric Rashes in Febrile PatientsPurpura fulminans and DIC are acutely life-threatening dis-orders that require emergency hematology consultation and ICU admission. First-line therapy is treatment of the underly-ing cause. Folate, vitamin K, fresh frozen plasma, cryopre-cipitate, platelets, and red blood cell transfusions are given as needed. Heparin is also used for associated thrombi. These patients are very ill, and use of these therapies is best done in

and wound care, topical steroids, and treatment of complications.

MACULOPAPULAR RASHESCentral Maculopapular Rashes in Febrile or Ill-Appearing PatientsThese patients usually have viral exanthems. They are typi-cally ill appearing with fever but are not moribund. Most patients respond to supportive care. Please refer to Chapter 18 for a discussion of pediatric exanthems.

Central Maculopapular Rashes in Well-Appearing PatientsThese patients may be having a drug reaction. Many drugs have been implicated: antibiotics, nonsteroidal antiinflamma-tory drugs (NSAIDs), chemotherapeutic agents, anticonvul-sants, and psychotropics, among others. Treatment includes discontinuation of the offending agent, and most care is sup-portive. Severe reactions, such as SJS, TEN, and hypersensi-tivity reactions, require hospital admission, meticulous wound care, and intensive support. Pityriasis is also in the differential diagnosis of well-appearing patients with central maculopap-ular rashes, and usually no treatment is required because it is generally a self-limited disease. For symptomatic pruritus, zinc oxide and calamine lotion are useful.

Peripheral Maculopapular Rashes in Febrile or Ill-Appearing Patients with Target LesionsThese patients may have EM major (refer to Table 191.2 for review). SJS and Lyme disease are also in the differential diagnosis. Treatment of SJS involves discontinuation of the offending agent, optimization of fluid and electrolyte balance, meticulous wound care, and ICU admission. For patients with Lyme disease, doxycycline is first-line treatment in nonpreg-nant adults. Children are treated with amoxicillin. Refer to Chapter 192 for further review of SJS and Lyme disease.

Peripheral Maculopapular Rashes in Febrile or Ill-Appearing Patients Without Target LesionsThese patients may have meningococcemia, RMSF, or syphi-lis. Patients with meningococcemia require intravenous cef-triaxone, with vancomycin added in cases of diagnostic uncertainty or to cover resistant streptococcal meningitis. Dexamethasone reduces neurologic sequelae if administered early and before antibiotics if possible. These patients also require admission and continuous surveillance for end-organ damage and complications. RMSF is always in the differential diagnosis in patients with these rashes or in those in whom meningococcemia is suspected. With any diagnostic uncer-tainty, one should treat for both illnesses. Doxycycline is the drug of choice in all nonpregnant patients with RMSF, even children. Pregnant patients may be treated with chlor-amphenicol, although doxycycline should also be considered because it is simply more effective. Secondary syphilis is also a diagnostic possibility in these patients and should be treated with intramuscular penicillin G in all patients. Benza-thine penicillin should not be used because it does not penetrate cerebrospinal fluid. Pregnant patients allergic to penicillin should undergo desensitization. Nonpregnant, penicillin-allergic patients may be treated with doxycycline.

Fig. 191.7 Eczema.

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immunocompromised patients and those with ocular involve-ment or disseminated disease and is recommended for indi-viduals older than 50 years, especially those with significant pain. High-risk patients require intravenous acyclovir, judi-cious administration of corticosteroids, ophthalmologic con-sultation (eye involvement), fluid and electrolyte monitoring, pain management, and supportive care. Treatment of dyshi-drotic eczema was reviewed in the section on maculopapular rashes. Treatment of burns depends on the type, whether induced by trauma, chemicals, radiation, or heat. Treatment is also guided by the depth, severity, and surface area involved. Severe burn injuries are treated with intravenous fluid admin-istration, early intubation (for airway involvement), removal or neutralization of the source of the injury, meticulous wound care, pain management, surgical intervention (early skin grafts or flaps, débridement, or escharotomy), and adjunctive hyperbaric oxygen therapy.

FOLLOW-UP AND PATIENT EDUCATION

PATIENTS WITH ERYTHEMATOUS RASHESFollow-up is dependent on the cause of the rash, the patient’s baseline immunologic health, disease complications, treat-ment side effects, and patient resources. Toxic patients with an erythematous rash require admission, intensive treatment, and close follow-up because all these diseases are associated with either very high morbidity and mortality or the potential for devastating complications. Patients with TSS require edu-cation regarding infective bacterial material. Those with SSSS, erythroderma, TSS, and TEN require close surveillance for secondary infections and wound care therapy. Patients with Kawasaki syndrome and scarlet fever require pediatric or primary care follow-up for monitoring of complications. Patients with severe exposure reactions (anaphylaxis and vancomycin) require intensive treatment, critical care moni-toring, and close follow-up for complications related to end-organ damage or the exfoliative dermatitis associated with vancomycin-induced erythroderma. Less serious exposure reactions (scombroid and alcohol flush) require primary care follow-up and patient education regarding exposure toxicities.

PATIENTS WITH MACULOPAPULAR RASHESPatients with viral exanthems, drug reactions, and scabies have self-limited illnesses and benefit by close follow-up and patient education with their primary care provider regarding exposures and potential complications. Those with eczema, psoriasis, or pityriasis should be referred to a dermatologist for initial consultation and primary care follow-up. Patients with SJS or EM require close outpatient management for complications and wound care follow-up. Those with menin-gococcemia, RMSF, Lyme disease, or syphilis require primary care follow-up in conjunction with infectious disease consul-tation and monitoring.

PATIENTS WITH PETECHIAL/PURPURIC RASHESPatients with meningococcemia, disseminated gonococce-mia, RMSF, and endocarditis require close primary care

consultation with the ICU team and a hematologist. TTP is a devastating disease with greater than 90% mortality if not treated properly. Treatment includes emergency hematol-ogy consultation, treatment of the underlying cause, fresh frozen plasma (as a temporizing measure), plasmapheresis, and ICU admission. It is important to avoid platelet ad -ministration because it will precipitate more thrombus for-mation. Exchange transfusions can reduce mortality to 10%, and facilities without these capabilities should consider early transfer. Please refer to Chapter 192 for further review of purpura fulminans/DIC and TTP.

Petechial/Purpuric Rashes in Afebrile PatientsThese patients may have a vasculitis (palpable rash) or ITP (nonpalpable rash). Please refer to Table 191.3 and Box 191.2 for reviews of these petechial/purpuric rashes.

VESICULOBULLOUS RASHESFebrile Patients with a Diffuse RashThese patients may have varicella, smallpox, disseminated gonococcemia, or purpura fulminans/DIC. Varicella is a childhood viral exanthem (chickenpox) that is intensely pru-ritic. Treatment is supportive and consists of wet dressings, soothing baths, calamine lotion, surveillance for secondary infection, and antihistamines. The role of acyclovir in healthy children is unclear. Immunocompromised patients are at risk for significant complications. Maternal infection in the first trimester may result in devastating congenital varicella syn-drome, whereas perinatal maternal infection predisposes to disseminated neonatal herpes. Smallpox is a dreaded variola infection against which 50% of the U.S. population has not been vaccinated. Care is supportive, and all personnel with smallpox exposure require quarantine and vaccination. The mortality rate is 30% in those who are unvaccinated. Treat-ment of disseminated gonococcemia is reviewed in Table 191.3. Treatment of purpura fulminans/DIC was reviewed with petechial/purpuric rashes. Please refer to Chapter 18 for review of varicella and Chapter 192 for review of smallpox and purpura fulminans/DIC.

Febrile Patients with a Localized RashNecrotizing fasciitis is in the differential diagnosis for these patients. It is an acutely toxic bacterial infection with very high mortality. Treatment consists of prompt surgical débride-ment, broad-spectrum antibiotics, and adjunctive hyperbaric oxygen therapy. Hand-foot-and-mouth disease is a highly con-tagious viral illness that requires symptomatic care for the painful oral ulcers. Complications are rare; however, infection during the first trimester of pregnancy may result in spon-taneous abortion. Please refer to Chapter 192 for review of necrotizing fasciitis and Chapter 18 for review of hand-foot-and-mouth disease.

Afebrile Patients with a Diffuse RashThese patients have either BP or PV. Both these diseases and their treatments are reviewed in Table 191.4.

Afebrile Patients with a Localized RashThese patients may have herpes zoster, dyshidrotic eczema, or a local burn. Herpes zoster or shingles (caused by varicella virus) is a self-limited illness that will resolve without intervention. However, treatment is required for

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follow-up, as well as infectious disease consultation and monitoring. Additionally, follow-up of endocarditis should include cardiologist involvement. Patients with HSP should be monitored by their primary care physician for resolution of symptoms and for complications. Patients with purpura fulminans/DIC, ITP, and TTP must be monitored by a pri-mary care provider, a hematologist, and a wound care spe-cialist as needed. Those with vasculitis benefit from continued monitoring by their primary care provider, with dermatology consultation and wound care as appropriate.

PATIENTS WITH VESICULOBULLOUS RASHESPatients with varicella, hand-foot-and-mouth disease, herpes zoster, dyshidrotic eczema, and contact dermatitis benefit from close primary care follow-up for pain control and moni-toring for complications. Patients with smallpox, dissemi-nated gonococcemia, and necrotizing fasciitis should follow up with their primary care physician, an infectious disease specialist, and a wound care specialist as needed. Patients with necrotizing fasciitis should also receive follow-up from their attending surgeon. Patients with purpura fulminans/DIC require close monitoring for continued improvement by a primary care physician and a hematologist. Wound care may be needed. Those with BP and PV benefit from close primary care follow-up, as well as dermatologic consultation and wound care.

RED FLAGS

Feverandpetechiae/purpuraMucousmembraneinvolvementHemorrhagicbullaeNikolskysignNonpalpablepetechiaewithneurologicsymptoms

SUGGESTED READINGSCarr DR, Houshmand E, Heffernan MP. Approach to the acute, generalized, blistering

patient. Semin Cutan Med Surg 2007;26:139-46.Mukasa Y, Craven N. Management of toxic epidermal necrolysis and related

syndromes. Postgrad Med J 2008;84:60-5.Murphy-Lavoie H, LeGros T. Emergent diagnosis of the unknown rash, the

algorithmic approach. Emerg Med 2010;42(3):6-17.Nguyen T, Freedman J. Dermatologic emergencies: diagnosing and managing

life-threatening rashes. Emerg Med Pract 2002;4:1-28.Rothe MJ, Bernstein ML, Grant-Kels JM. Life-threatening erythroderma: diagnosing

and treating the “red man.” Clin Dermatol 2005;23:206-17.

REFERENCES

References can be found on Expert Consult @ www.expertconsult.com.

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an algorithmic approach. Emerg Med 2010;42(3):6-17.2. Mukasa Y, Craven N. Management of toxic epidermal necrolysis and related

syndromes. Postgrad Med J 2008;84:60-5.3. Nguyen T, Freedman J. Dermatologic emergencies: diagnosing and managing

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6. Gupta S, Handa S, Kanwar A, et al. Cutaneous vasculitides: clinico-pathological correlation. Indian J Dermatol Venereol Leprol 2009;74:356-62.

7. Ekenstam E, Callen JP. Cutaneous leukocytoclastic vasculitis—clinical and laboratory features of 82 patients seen in private practice. Arch Dermatol 2006;120:484-9.

8. Marieke Schoonen W, Kucera G, Coalson J, et al. Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database. Br J Haematol 2009;145:235-44.

9. Carr DR, Houshmand E, Heffernan MP. Approach to the acute, generalized, blistering patient. Semin Cutan Med Surg 2007;26:139-46.

10. Chan L. Bullous pemphigoid. eMedicine. Available at http://emedicine.medscape.com/article/1062391-overview. Updated November 20, 2009.