EMERGENT DIAGNOSIS OF THE

AN ALGORITHMIC APPROACH

Clinicians must rapidly determine whether a is dangerous—or even life-threatening—and act quickly to reduce the risk for mortality.

Heather Murphy-Lavoie, MD, FAAEM, and Tracy Leigh LeGros, MD, PhD, FACEP, FAAEM

onsider this clinical vignette: An ob- tous skin that is sloughing off in large sheets (Figure tunded man with limited ability to pro- 1). He appears very dehydrated, with oral mucous vide a pertinent history presents to the membrane involvement. What is your differential ED at 2 AM. The nurse states that the diagnosis at this point? Cman “may have been burned.” Vital signs at triage Although thermal is in the differential di- included a heart rate of 120 beats/min; respiratory agnosis, this patient has toxic epidermal necrolysis rate, 24 breaths/min; and temperature, 37.7ºC. In ad- (TEN), which is characterized by erythematous skin dition, a blood pressure of 110/60 mm Hg and pulse and sloughing and has a mortality of 30% to 35% oxygenation of 98% were recorded. Your assessment with optimal treatment.1 Early recognition is critical. finds the patient is a lethargic and toxic-appearing man about 45 years of age, with diffusely - INTRODUCTION According to 2006 data, rash is among the top 20 Dr. Murphy-Lavoie is assistant clinical professor in reasons for ED visits in the United States.2 This ar- the section of emergency medicine at Louisiana State ticle presents a set of novel and easily interpreted al- University Health Sciences Center in New Orleans, gorithms designed to guide the emergency physician where she is also the assistant director of the emergency medicine residency program and associate director of the in identifying the most common—and potentially undersea and hyperbaric medicine fellowship program. lethal—rash syndromes. While an exhaustive review Dr. LeGros is assistant clinical professor in the section of of all pediatric , endemic fungal etiolo- emergency medicine at Louisiana State University Health Sciences Center, where she is also the director of the gies, and parasitic exanthems is beyond the scope of

undersea and hyperbaric medicine fellowship program. this article, the algorithms presented here will equip Inc. © Photo Researchers,

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the emergency physician to quickly recognize the most common and critical . Table 1 depicts common terms associated with the diagnosis of a rash. Table 2 categorizes rash syndromes according to patient characteristics and presenting symptoms. Following the presentation of the algorithms, we review the salient points of the most clinically im- portant diseases.

HISTORY When taking a history from a patient with a rash, the clinician should elicit information about the following:

Onset and Progression The distribution and progression of the rash are essential features. The vasculidities generally begin peripherally and spread centrally. Rocky Mountain spotted (RMSF) classically starts on the wrists/ ankles and spreads centripetally. Viral rashes usually begin centrally and progress peripherally.3 Rashes of the palms and soles can be drug induced or infectious (eg, target lesions of [EM], sec- FIGURE 1. Toxic epidermal necrolysis. ondary , RMSF). Localized lesions may repre- sent a contact or infectious process. Most deadly rashes progress rapidly. Urticaria disease are at increased risk for endocarditis. College with anaphylaxis can spread within minutes. The students, military personnel, and employees of day petechiae associated with meningococcemia appear care facilities are more likely to contract meningo- after toxicity has begun and progress within hours. coccemia. Hunters and campers are at risk for - Drug reactions may develop over days. borne illnesses.

Travel History Regimens It is important to determine if the patient has re- Determine which the patient is tak- cently traveled. is common in the mid- ing. Potentially lethal drug reactions such as SJS, Atlantic, central, western, and northeastern parts of TEN, anaphylaxis, and mandate specific the United States. Toxic patients who have recently and emergent interventions. Additionally, many pa- traveled to the Caribbean may have . tients self-treat rashes prior to presentation. Steroid And, of course, patients reporting recent camping creams, in particular, may significantly alter rash and travel through wooded areas are candidates for morphology.3 RMSF. PHYSICAL EXAMINATION POINTERS Medical or Occupational History To begin, it is essential to evaluate vital signs. Fe- Those with diabetes, HIV, a history of intravenous ver and hypotension, in particular, are ominous drug abuse, and patients undergoing chemother- findings that mandate expedited and intensive care. apy are at risk for diseases of high morbidity and Additional physical exam findings of concern in- mortality: meningococcemia, thrombotic thrombo- clude new-onset heart murmur or nuchal rigidity. cytopenic (TTP), necrotizing fasciitis, dis- Generalized lymphadenopathy is present in many seminated zoster, EM, Stevens-Johnson Syndrome illnesses, including mononucleosis and other infec- (SJS), TEN, and sepsis. Persons with valvular heart tions, serum sickness, and drug reactions. www.emedmag.com MARCH 2010 | EMERGENCY MEDICINE 7 UNKNOWN RASH

TABLE 1. Common Terms Used in Rash Diagnosis Lesion Single small, diseased area Rash An eruption on the skin; more extensive than a single lesion Macule Circumscribed area of change without elevation Pustule Circumscribed area containing pus

Papule Solid raised lesion ≤1 cm Vesicle Circumscribed fluid-filled area ≤1 cm Nodule Solid raised lesion ≥1 cm Bulla Circumscribed fluid-filled area Plaque Circumscribed elevated ≥1 cm confluence of ≥1 cm Petechia Small red/brown macule ≤1 cm that does not blanche

TABLE 2. Clues Toward a Definitive Diagnosis

Clues to Diagnosis Rash

Patient Age 0 to 5 years Meningococcemia, , viral

>65 years  vulgaris, sepsis, meningococcemia, TEN, SJS, TSS

Rash Characteristics Diffuse erythema Staphylococcal SSS, staphylococcal or streptococcal TSS, necrotizing fasciitis

Mucosal lesions EM major, TEN, SJS,

Petechiae/purpura Meningococcemia, necrotizing fasciitis, , DIC, RMSF

Symptom

Hypotension Meningococcemia, TSS, RMSF, TEN, SJS

TEN = toxic epidermal necrolysis; SJS = Stevens-Johnson syndrome; TSS = toxic shock syndrome; SSS = scalded skin syndrome; EM = erythema multiforme; DIC = disseminated intravascular coagulopathy; RMSF = Rocky Mountain spotted fever.

Thorough Examination for signs of systemic disease or fungal . Ad- To ensure that lesions on the back, buttocks, or ditionally, the soles and palms should be examined. perineum are identified, patients should be com- pletely undressed for the examination. Often, pa- Mucous Membrane Involvement tients are unaware of lesions that are present in these Dysphagia, eye, or genital irritation may represent mu- locations. The patient’s shoes and socks should also cosal involvement and possibly indicate a life-threat- be removed (especially in diabetic persons), as sig- ening condition such as TEN, SJS, or pemphigus nificant bacterial and fungal may be pres- vulgaris. Conjunctival injection is often also associated ent on the feet. Toenails should be closely inspected with viral syndromes, as well as with Kawasaki disease.

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FIGURE 2. Diagnosis of the Erythematous Rash

Erythematous rash

Nikolsky sign Yes No

Febrile Afebrile Febrile Afebrile

Staphylococcal SSS TEN TSS (mucous Anaphylaxis (children) membranes) Scombroid poisoning TEN (adults) Kawasaki disease Alcohol flush (children; swollen hands) (“sandpaper rash”)

SSS = scalded skin syndrome; TEN = toxic epidermal necrolysis; TSS = toxic shock syndrome.

Specific Signs staphylococcal SSS presents as a scarlatiniform, The Nikolsky sign is a sloughing of full-thickness erythematous rash that and sloughs (posi- skin with lateral pressure. The Asboe-Hansen sign is tive Nikolsky sign). Children younger than 5 years a that spreads into clinically normal skin with are at highest risk. Patients initially have an abrupt light lateral pressure. Both are seen in TEN, as well fever, erythema of the neck, axillae, and groin, and as in other conditions. It is also important to look extreme skin tenderness. Diagnostic clues include for blanching in the diagnosis of petechial rashes.3 a lack of mucous membrane involvement and a skin cleavage plane that is more shallow than that THE ALGORITHMIC APPROACH associated with TEN. Treatment of this infec- Erythematous Rashes tion includes antistaphylococcal , fluid Characterized by diffuse redness of the skin due to and electrolyte management, and local wound capillary congestion, erythematous rashes (Figure 2, care. Young, well-appearing patients with minimal page 9) are differentiated from other rashes based skin sloughing may be managed as outpatients. In on the presence or absence of fever and the Nikol- young children, this disease has a mortality of less sky sign. If these factors are present, the diagnosis is than 5%; in contrast, this disease is very rare in narrowed substantially, usually to TEN in adults and adults, but when it occurs, mortality can be as high staphylococcal scalded skin syndrome (SSS) in in- as 60%.4,5 fants and young children. If fever is present without the Nikolsky sign, the includes Toxic Epidermal Necrolysis: TEN, also known as Kawasaki disease, scarlet fever, and toxic shock syn- Lyell disease, is the most serious cutaneous drug drome (TSS). Those patients with an erythematous reaction and most commonly associated with rash but without a fever or Nikolsky sign may be sulfa drugs. Other important triggers include an- having an anaphylactic reaction or an exposure reac- ticonvulsants, antivirals, NSAIDs, and . tion to scombroid or alcohol. TEN presents as sudden-onset diffuse erythema with tender skin and sloughing. Symptoms oc- Staphylococcal Scalded Skin Syndrome: Known as cur first on the face and around the eyes, spread Ritter disease or dermatitis exfoliativa neonatorum,4 caudally to the shoulders and upper extremities, www.emedmag.com MARCH 2010 | EMERGENCY MEDICINE 9 UNKNOWN RASH

FIGURE 3. Diagnosis of the Maculopapular Rash

Maculopapular rash

Central Peripheral distribution distribution

Fever/ill Fever/ill

Yes No Yes No

Viral exanthem Drug reaction Target Lesion lesions distribution Lyme disease (erythema (herald patch) migrans)

Flexor Extensor

Scabies Eczema

Yes No

SJS Meningococcemia Erythema RMSF multiforme Syphilis Lyme disease ()

SJS = Stevens-Johnson syndrome; RMSF = Rocky Mountain spotted fever.

and then progress to the whole body. The skin At-risk populations include those with head in- cleavage is full thickness (positive Nikolsky and juries, brain tumors, systemic erythematosus Asboe-Hansen signs), with massive skin slough- (SLE), and immunocompromise.6 Importantly, HIV ing in large sheets. Patients with TEN are toxic, patients have a TEN risk that is 1,000 times greater with myalgias and substantial mucous mem- than that in patients without HIV.6 brane involvement. The mortality of TEN is Treatment consists of discontinuation of the of- considerable—30% to 35% with optimal care.1 fending agent, wound care, eye care, and fluid and

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electrolyte resuscitation. Intravenous immune glob- diagnosis; however, it is paramount that patients liv- ulin (IVIG) may be helpful, although it is not yet ing in endemic areas be assessed for Lyme disease. FDA approved for this indication. Most physicians Those with centrally distributed rashes but without recommend against steroid use. Sulfadiazine should signs of toxicity usually present with either a drug not be used on the wounds, as sulfa is the most com- reaction or . Patients with peripher- mon offending agent.7 Patients with TEN usually ally distributed rashes have a broader differential di- require ICU admission and should be managed in a agnosis, which is dependent upon systemic toxicity, burn unit if skin sloughing is extensive. presence or absence of target lesions, and whether the rash is located on the flexor or extensor surfaces. Toxic Shock Syndrome: This toxin-mediated staph- Target lesions are for SJS or EM. ylococcal or streptococcal infection is historically Patients with peripheral lesions and systemic toxicity associated with tampon use, although any staphy- but without target lesions require emergent evalua- lococcal or streptococcal source can precipitate tion for meningococcemia, RMSF, and syphilis. Non- TSS. Up to 45% of cases are unrelated to menses; toxic patients with a peripherally distributed rash but TSS can be associated with , nasal pack- without target lesions require further assessment for ing, surgical wounds, and postpartum conditions.3 flexor involvement ( or eczema) or extensor Patients are overtly toxic, in shock, and febrile, with involvement (psoriasis). a diffuse erythematous rash that eventually leads to desquamation of the hands and feet. Treatment Lyme Disease: This tick-borne illness is caused by includes removal of the infective material, admin- burgdorferi. The patient generally presents istration of IV antibiotics, fluid resuscitation and, with erythema migrans (a large annular lesion with possibly, IVIG. Patients with TSS require ICU dark red border and central clearing) at the site of admission. the tick bite. This rash begins with tick inoculation and therefore may be central or peripheral.3 As the Kawasaki Disease: This childhood illness is also rash spreads hematogenously over days to weeks, the known as mucocutaneous lymph node syndrome or in­ patient may experience a variety of systemic symp- fantile polyarteritis. Kawasaki disease is a vasculitis of toms, including a secondary skin rash (annular le- unknown cause, although infective and autoimmune sions), fever, , atrioventricular nodal block, theories abound. It affects many systems, including migratory , and myalgias. occurs the skin, mucous membranes, lymphatics, and blood as well, often manifesting as Bell’s palsy (which may vessels. Diagnostic criteria include high fever for at be bilateral); however, any nerve can be affected. The least 5 days, diffuse , strawberry tongue, diagnosis is made clinically, although a of the significant cervical lymphadenopathy, conjunctival of the site of the tick bite is often diagnostic. Sero- injection, peeling of the fingers and toes, and edema logic tests are positive after several weeks but do not of the extremities.8 By far the most serious complica- differentiate active from inactive infection. Doxycy- tion is vasculitis of the coronary arteries, leading to cline is the first-line treatment in nonpregnant adult coronary vessel aneurysms and myocardial infarction, patients. Children may be treated with amoxicillin. even in young children. Treatment comprises high- dose (given immediately), hospitalization with Stevens-Johnson Syndrome: This condition often supportive care, and (very importantly) IVIG. Kawa- occurs as a drug reaction, although infections and saki disease does not respond to antibiotics.8,9 malignancies have been implicated. Previously, SJS was thought to be linked with EM, but recently it has Maculopapular Rashes been reclassified with TEN.6 Patients present with The term maculopapule is a portmanteau, a combina- diffusely distributed target lesions that include the tion of macule and (Table 1, page 8). Macu- palms and soles, as well as mucous membrane involve- lopapular rashes are differentiated based on the ment. These patients are toxic, with many constitu- distribution of the rash and systemic toxicity (Figure 3, tional symptoms. Treatment involves discontinuation page 10). Patients with centrally distributed rashes of the offending agent and optimizing fluid and elec- who appear toxic and febrile have a wide differential trolyte levels. Use of steroids is considered controver- www.emedmag.com MARCH 2010 | EMERGENCY MEDICINE 11 UNKNOWN RASH

FIGURE 4. Diagnosis of the Petechial/Purpuric Rash

Petechial/purpuric rash

Febrile, toxic Afebrile, nontoxic

Palpable Nonpalpable Palpable Nonpalpable

Meningococcemia Purpura Autoimmune Idiopathic fulminans vasculitis thrombocytopenic Disseminated purpura gonococcal DIC infection TTP Endocarditis RMSF Henoch-Schönlein purpura

RMSF = Rocky Mountain spotted fever; DIC = disseminated intravascular coagulopathy; TTP = thrombotic .

sial. Both SJS and TEN have greater mortality (10% brane involvement. Prodromal symptoms (eg, mild, and 30%, respectively) than do EM major (mortality nonspecific upper respiratory tract infection, mod- less than 5%) and minor (negligible morbidity). Pa- erate fever, general discomfort, cough, sore throat, tients with SJS require ICU admission.1,5-7,10 , chest pain, ) occur 1 to 2 weeks prior to the onset of rapidly progressive lesions that Erythema Multiforme: This condition may present spread centripetally. The rash is maculopapular and as a mild, self-limited rash (EM minor) or a severe, nonpruritic; it evolves into target lesions on the life-threatening disease with significant mucous palms, soles, dorsa of the hands, face, and extensor membrane involvement (EM major).6 The etiol- surfaces. Eye involvement occurs in 10% of cases, ogy cannot be identified in up to 50% of affected often as a bilateral purulent conjunctivitis. Diagno- patients, but EM is thought to be autoimmune in sis is confirmed by biopsy. Mild cases (EM minor) nature and usually follows infection (, require only symptomatic support (analgesics, cold Mycoplasma, fungal diseases) or drug exposure (sulfa compresses, topical steroids), treatment of cause (if drugs, anticonvulsants, antibiotics). The mild form identified), and outpatient dermatologic follow-up. presents as pruritic, symmetrically arranged lesions Erythema major requires more aggressive care, with on the extremities that develop into classic target discontinuation of the offending agent, fluid and lesions; these resolve in 1 to 2 weeks. This rash does electrolyte balance, analgesics, wound care similar not involve the mucous membranes. EM major pres- to that of thermal ( should ents with target lesions and significant mucous mem- be avoided), and soothing solutions for oral le-

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sions.3 The use of systemic steroids is of unproven a mortality greater than 30%; this decreases to 5% benefit and may increase complications. Dermato- with prompt therapy. Permanent neuro- logic consults are required for admitted patients, as logic deficits persist in 15% of cases.11-15 are ophthalmologic consults for those with ocular is the drug of choice in all nonpregnant patients, involvement.3 even children. Pregnant patients may be treated with chloramphenicol.3,11-15 Meningococcemia: Infection with Neisseria meningi­ tidis has a predilection for adolescents and children Petechial/Purpuric Rashes younger than 4 years. Without proper treatment, These rashes can be especially challenging and are meningococcemia is invariably fatal; mortality associated with devastating differential diagnoses; remains at 10% to 20%, even with immediate however, an algorithmic approach can help the physi- therapy.3 Patients are ill appearing, febrile, and in cian narrow the diagnosis with confidence (Figure 4, shock, with mental status changes and a rash that page 12). Additionally, remembering the etiology of develops within 24 hours of toxicity. The rash is ini- palpable versus nonpalpable lesions is paramount. tially erythematous and maculopapular (beginning Palpable (raised) purpura occurs in vasculitic dis- on wrists and ankles); it then spreads and becomes eases secondary to or infection. Non- petechial. Early in the illness, meningococcemia palpable purpura presents in thrombocytopenic can be mistaken for RMSF. Treatment for both is conditions (flat, subcutaneous hemorrhages). Pa- mandatory when there is any diagnostic uncertainty. tients with petechiae/purpura with fever or toxic- Diagnosis is confirmed by Gram stain and blood ity require emergent evaluation. If the lesions are and/or cerebrospinal fluid (CSF) cultures. Gram palpable, the differential diagnosis includes menin- staining of a specimen from a meningococcal skin gococcemia, disseminated gonococcal disease, en- lesion is more sensitive than a CSF Gram stain docarditis, RMSF, and Henoch-Schönlein purpura. (72% vs 22%, respectively).3 Ceftriaxone is first- Those with petechiae/purpura with fever/toxicity line therapy. should be added in cases but with nonpalpable lesions may have purpura of diagnostic uncertainty to cover resistant strepto- fulminans, disseminated intravascular coagulopathy coccal meningitis. Dexamethasone has been shown (DIC), or TTP. If the patient is afebrile with a pe- to reduce neurologic sequelae if administered early techial or purpuric rash, the diagnosis may be far (prior to antibiotics, if possible). Rifampin prophy- simpler and less ominous. Nontoxic patients with laxis for persons in close contact with the patient palpable lesions may have a vasculitis, such as auto- is recommended; alternatives include single-dose immune vasculitis; those with nonpalpable lesions ciprofloxacin and IM ceftriaxone.3 may have idiopathic thrombocytopenic purpura. While all patients with petechiae require complete Rocky Mountain Spotted Fever: Another tick-borne assessment, those with nonpalpable petechiae are illness (Rickettsia rickettsii), RMSF occurs primar- more likely to have thrombocytopenia. ily in the south-Atlantic region and also occurs in other regions of the United States. Only 50% of Henoch-Schönlein Purpura: Also known as allergic affected patients can recall being bitten by a tick.3 purpura or anaphylactoid purpura, this disease is found The erythematous maculopapular rash begins on mainly in children. It is an autoimmune systemic the wrists and ankles and spreads over the body. In vasculitis affecting primarily the skin (usually on the its early stage, the rash presents as reddish macules legs, buttocks, and arms) and kidneys. It is often that blanch, only to become petechial and purpuric preceded by an infection or drug exposure. The later. In up to 20% of patients, the rash is absent classic triad associated with this disease comprises (spotless fever).3 Regardless of rash presence or ab- purpura, abdominal pain, and arthritis (particularly sence, the patient will be highly febrile and toxic. in the knees, ankles, and elbows). The purpura is For RMSF, the diagnosis is made clinically. Physi- palpable and pruritic. The abdominal pain may be cians should not wait for confirmatory antibody test associated with , vomiting, intussusception, results before beginning treatment, as these will be diarrhea, or constipation. Hematuria is classic and negative in the acute period. If untreated, RMSF has occurs in 10% to 20% of cases; however, less than www.emedmag.com MARCH 2010 | EMERGENCY MEDICINE 13 UNKNOWN RASH

FIGURE 5. Diagnosis of the Vesiculobullous Rash

Vesiculobullous rash

Febrile Afebrile

Diffuse Localized Diffuse Localized distribution distribution distribution distribution

Varicella Necrotizing Bullous Contact fasciitis pemphigoid dermatitis Hand-foot- Pemphigus Herpes zoster Disseminated and-mouth vulgaris gonococcal disease Dyshidrotic disease eczema Burns DIC

DIC = disseminated intravascular coagulopathy.

1% of children go on to develop end-stage renal schistocytes, prolonged prothrombin time (PT) and disease.16 Most patients require only supportive partial thromboplastin time (PTT), increased fibrin care, although relapses occur. Some patients require degradation products, increased D-dimer levels, and hospitalization for pain control, kidney biopsy, and/ decreased fibrinogen levels. Emergent hematology/ or administration of immunosuppressant agents or, oncology consult and ICU admission are manda- occasionally, IVIG. The use of steroids is contro- tory. First-line therapy is treatment of the under- versial. The prognosis is good, with full recovery lying cause. Folate, vitamin K, fresh frozen plasma in more than 80% to 90% of patients; permanent (FFP), cryoprecipitate, platelets, and kidney damage is rare. transfusions are given as needed; heparin is used for associated thrombi. It may be necessary to initiate Purpura Fulminans: This acutely life-threatening these treatments in the ED if the patient cannot be disorder is associated with previous infection (most admitted immediately to the ICU. However, treating commonly meningococcal or gram-negative organ- this disease is a tricky balancing act that is best done isms), pregnancy, massive trauma, end-stage malig- in consultation with a hematologist.17,18 nant disease, hepatic failure, , transfusion reactions, and anything else that may precipitate DIC. Thrombotic Thrombocytopenic Purpura: Patients It is characterized by fever, shock, rapid subcutane- with this disease present with a diffuse, nonpalpable ous hemorrhage (ecchymotic purpura/hemorrhagic petechial/purpuric rash. The classic pentad of symp- bullae), tissue necrosis, widespread petechiae, bleed- toms includes fever, thrombocytopenia, hemolytic ing from multiple sites, widespread organ failure, and anemia, neurologic deficits, and renal failure; how- DIC. Laboratory findings include thrombocytopenia, ever, it is more common to observe the clinical triad

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of thrombocytopenia, hemolytic anemia, and elevated lactate dehydrogenase. These findings alone are suf- ficient for the diagnosis and initiation of treatment. There are numerous associated conditions, including HIV, SLE, pregnancy, malignancy, and transplanta- tion. Unlike those with DIC, patients with TTP often have normal PT/PTT and fibrin values. Schis- tocytes and helmet cells, indicating hemol­ysis, are seen on blood smears. Treatment includes emergent hematology/oncology consultation, plasmapheresis, FFP, and treatment of the underlying cause. Impor- tantly, FFP can be used as a temporizing measure, but patients with TTP should be transferred to a facility with plasmapheresis capabilities. Mortality FIGURE 6. Bullous pemphigus. is less than 10% when plasmapheresis is used; it is more than 90% without such treatment.19,20 Platelets Pemphigus is associated with other autoimmune dis- should not be administered, as they will precipitate orders, especially myasthenia gravis and thymoma. additional thrombus formation.19 Triggers include penicillamine, captopril (or other thiol-containing compounds), rifampin, and emo- Vesiculobullous Rashes tional stress. The diagnosis is made clinically with Vesiculobullous rashes provoke significant angst confirmation by biopsy. Patients with large areas of in many physicians (Figure 5, page 14). However, involvement require admission for fluid and electro- the differential diagnosis can be greatly simplified lyte balance, pain control, monitoring for secondary by categorizing patients with these rashes as febrile infection, and treatment with immunosuppressant or afebrile and noting whether the rash distribu- drugs.5,21 Although pemphigus had a mortality rate tion is diffuse or localized. Patients with a diffuse of 50% to 90% before the advent of steroids, steroid vesiculobullous rash and a fever may have varicella therapy has reduced the mortality to 10% to 20%.3 or a more devastating illness, such as smallpox, dis- seminated gonococcal disease, purpura fulminans, or Bullous Pemphigus: This condition is a chronic, au- DIC. Necrotizing fasciitis and hand-foot-and-mouth toimmune cutaneous blistering that classically occurs disease present with localized lesions and fever. In in the elderly (average age, 65 years). Curiously, the afebrile patients with a diffuse vesiculobullous rash, incidence of infant BP appears to be rising. It has a the differential diagnosis includes bullous pemphi- better prognosis and notably less oral involvement gus (BP) and pemphigus vulgaris. These entities are than does pemphigus vulgaris; only 10% to 25% of regularly confused, and it is essential to differentiate patients with BP have oral involvement.5 However, urgently. However, the differential diagnosis is sim- the disease may persist for months or years (wax- pler and less emergent in a patient who is afebrile ing and waning) and may be fatal in frail patients. with a localized vesiculobullous rash; contact der- This disease has many triggers, including lichen matitis, herpes zoster, dyshidrotic eczema, and burns planus, psoriasis, radiation, x-ray therapy, (chemical or thermal) are included. and exposure to drugs such as furosemide, ibupro- fen, captopril, penicillamine, and certain antibiotics Pemphigus Vulgaris: Occurring primarily in per- and childhood vaccines. The rash is generalized and sons ages 50 to 60 years, this disease is a generalized bullous (Figure 6). The diagnosis is established by mucocutaneous autoimmune blistering with a poor histopathologic analysis of specimens taken from the prognosis. Most patients (60%) have mucosal surface blistering edge of the wounds. Treatment options in- involvement initially, which progresses to nonpru- clude oral and topical steroids, , immu- ritic skin blisters.5 The bullae coalesce and may pro- nosuppressive agents, dapsone, and supportive care. duce skin sloughing similar to that found in TEN or Dermatologic consultation is required, as is otolar- SSS, with positive Nikolsky and Asboe-Hansen signs. yngologic consultation for patients with mucosal in- www.emedmag.com MARCH 2010 | EMERGENCY MEDICINE 15 UNKNOWN RASH

16. Bossart P. Henoch Schonlein purpura. eMedicine. http:// volvement. In addition, ophthalmologic consultation emedicine.medscape.com/article/780452-diagnosis. Updated is warranted for patients with ocular involvement or June 18, 2009. Accessed February 13, 2010. for those who are taking a prolonged course of high- 17. Levi M. Disseminated intravascular coagulation. Crit Care Med. 2007;35(9):2191-2195. 21 dose steroids. 18. Levi M, de Jonge E, van der Poll T, ten Cate H. Novel approaches to the management of disseminated intravascular coagulation. Crit Care Med. 2000;28(suppl 9):20S-24S. CONCLUSION 19. Sarode R. Atypical presentations of thrombotic thrombocyto- After a comprehensive history has been taken and a penic purpura: a review. J Clin Apher. 2009;24(1):47-52. thorough physical examination has been performed, 20. Symonette D. Thrombotic thrombocytopenic purpura. eMedi- cine. http://emedicine.medscape.com/article/779969-overview. an algorithmic approach can be used to narrow the Updated September 16, 2009. Accessed February 13, 2010. differential diagnoses of the four most common cat- 21. Chan L. . eMedicine. http://emedicine .medscape.com/article/1062391-overview. Updated November egories of rashes. While the unknown rash can be 20, 2009. Accessed January 10, 2010. perplexing and anxiety provoking to the emergency physician, attention to simple differentiating char- acteristics (fever, toxicity, distribution, specific signs, target lesions, and palpability) can guide the physi- cian to the correct diagnosis. ■

REFERENCES 1. Ghislain PD, Roujeau JC. Treatment of severe drug reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis and syndrome. Dermatol Online J. 2002;8(1):5. 2. Centers for Disease Control and Prevention, DHHS Publication No. (PHS) 2008–1250, August 2008. National Hospital Ambula- tory Medical Care Survey: 2006 Emergency Department Sum- mary. National Health Statistics Report. http://www.cdc.gov/ nchs/data/nhsr/nhsr007.pdf. Accessed February 16, 2010. 3. Nguyen T, Freedman J. Dermatologic emergencies: diagnos- ing and managing life-threatening rashes. Emerg Med Pract. 2002;4(9):1-28. 4. Margileth AM. Scalded skin syndrome: diagnosis, differential diagnosis, and management of 42 children. South Med J. 1975;68(4):447-454. 5. Carr DR, Houshmand E, Heffernan MP. Approach to the acute, generalized, blistering patient. Semin Cutan Med Surg. 2007;26(3):139-146. 6. Mukasa Y, Craven N. Management of toxic epidermal necroly- sis and related syndromes. Postgrad Med J. 2008;84(988):60-65. 7. Chia FL, Leong KP. Severe cutaneous adverse reactions to drugs. Curr Opin Clin Immunol. 2007;7(4):304-309. 8. Hom C. Vasculitis and thrombophlebitis. eMedicine. http:// emedicine.medscape.com/article/1008239-overview. Updated November 23, 2009. Accessed January 10, 2010. 9. Yamamoto LG. Kawasaki disease. Pediatr Emerg Care. 2003;19(6):422-424. 10. Wolf R, Matz H, Marcos B, Orion E. Drug rash with eosinophilia and systemic symptoms vs toxic epidermal necrolysis: the dilemma of classification. Clin Dermatol. 2005;23(3):311-314. 11. Chapman AS, Murphy SM, Demma LJ, et al. Rocky mountain spotted fever in the United States, 1997-2002. Ann N Y Acad Sci. 2006;1078:154-155. 12. Centers for Disease Control and Prevention. Fatal cases of Rocky Mountain spotted fever in family clusters—three states, 2003. MMWR Morb Mortal Wkly Rep. 2004;53(19):407-410. 13. Archibald LK, Sexton DJ. Long-term sequelae of Rocky Moun- tain spotted fever. Clin Infect Dis. 1995;20(5):1122-1125. 14. Buckingham SC, Marshall GS, Schutze GE, et al. Clinical and laboratory features, hospital course, and outcome of Rocky Mountain spotted fever in children. J Pediatr. 2007;150(2):180-184. 15. Davis BP, Marx JA. An evidence-based approach to the diag- nosis and treatment of Rocky Mountain spotted fever in the emergency department. Emerg Med Pract. 2007;9(3):1-24.

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