Buka emergencies in dermatology

694 views

Published on

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
694
On SlideShare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
0
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Buka emergencies in dermatology

  1. 1. 19B. Buka et al. (eds.), Buka’s Emergencies in Dermatology,DOI 10.1007/978-1-4614-5031-3_2, © Springer Science+Business Media, LLC 20132.1 IntroductionWhile most infections with dermatological mani-festations are self-limited, there are clinical sce-narios when infectious cutaneous diseases areassociated with life-threatening systemic symp-toms. These diseases may be difficult to diagnose,but a dermatologist can use visual cues to create adifferential. The majority of infectious emergen-cies in dermatology are due to a bacterial patho-gen; however, select viruses, fungi, and parasitescan also cause severe disease.This chapter focuseson cutaneous infections where prompt diagnosisand initiation of treatment are paramount. Wehighlight the main cutaneous patterns, individualsat risk, diagnostic modalities applicable to thedermatologist, and treatment options for eachinfectious emergency in dermatology.2.2 Bacterial Infections2.2.1 Necrotizing FasciitisNecrotizing fasciitis is characterized by rapidlyprogressive necrosis of subcutaneous fat and fas-cia. In many cases, no identifiable cause is found;however, patients often have a history of trauma[1]. Most patients have preexisting conditionsincreasing their susceptibility to infection, includ-ing immunosuppression, diabetes, chronic dis-ease, drugs (e.g., steroids), malnutrition, agegreater than 60, intravenous drug misuse, periph-eral vascular disease, renal failure, underlyingmalignancy, or obesity [2].Necrotizing fasciitis can be divided into threecategories based on etiologic agent. Type I is poly-microbial and can include Group A β-hemolyticStreptococcus Streptococcus pyogenes or GAS),Staphylococcus aureus, Klebsiella species,Enterococci, Escherichia coli, as well as Clostridiumand Bacteroides species. Type II is caused by GASonly and Type III is associated with Vibriovulnificus, which is introduced into the subcutane-ous tissue by puncture wounds from fish or marinecreatures [3].The initial clinical features may be nonspecific,often leading to misdiagnosis. Early findingsinclude pain, cellulitis, fever, tachycardia, swelling,induration, and skin anesthesia. As the infectionprogresses, severe pain out of proportion with theskinexamination,purpleorblackskindiscoloration,blistering, hemorrhagic bullae, crepitus, dischargeE. Stamell, M.D.(*)Department of Medicine, Division of Dermatology,Albert Einstein College of Medicine, Bronx,NY, USAe-mail: estamell@gmail.comK. Krishnamurthy, D.ODermatology, Jacobi Medical Center,Cosmetic Dermatology Clinic, Montefiore MedicalCenter, Albert Einstien College of Medicine, Bronx,NY, USAe-mail: kkderm@gmail.com2Infectious Emergenciesin DermatologyEmily Stamell and Karthik Krishnamurthy
  2. 2. 20 E. Stamell and K. Krishnamurthyof “dishwater,” or murky, grayish, fluid, severe sep-sis, systemic inflammatory response syndrome, ormultiorgan failure can develop [2]. The infectionrapidly evolves over hours or days.The pathognomonic finding of crepitus andsoft tissue air on plain radiograph is only seen in37% and 57% of patients, respectively. Crepitusresults from anaerobic tissue metabolism, whichproduces hydrogen and nitrogen, insolublegases, that accumulate in the subcutaneous tis-sues. Other common laboratory findings includeelevated white cell count, increased concentra-tions of serum glucose, urea, and creatinine,hypoalbuminemia, acidosis, and altered coagu-lation profile [4]. However, given the nonspecificnature of these studies, the diagnosis is clinical.Clinical signs that favor necrotizing fasciitisover cellulitis include presence of cutaneousanesthesia as it suggests a deeper component tothe infection affecting sensory nerves, severepain, rapidly spreading tense edema, hemor-rhagic bullae formation, gray-blue discoloration,and foul-smelling discharge [5].The mainstay of effective treatment is exten-sive surgical debridement in conjunction withbroad-spectrum antibiotics. Gram stain can guideappropriate antimicrobial therapy, but should notbe delayed while awaiting results. Initial ther-apy should include a b-lactam/b-lactamase inhib-itor combined with broad-spectrum coverageagainst Gram-negative bacilli, Staphylococci,Streptococci, and anaerobes. Antibiotics can betailored depending on the isolated organism(s).Table 2.1 outlines the antimicrobial algorithm fornecrotizing fasciitis [3]. Hyperbaric oxygen hasbeen postulated to decrease the number of debri-dements and mortality; however, no large studyhas confirmed this theory [6]. Intravenous immu-noglobulin (IVIG) has been used as an adjuvanttherapy primarily in patients with GAS necrotizingTable 2.1 Antimicrobial regimens for necrotizing fasciitis [3]Organism First-line therapyMixed Infections Ampicllin–sulbactam intravenous 1.5–3 g every 6 horPiperacillin–tazobactam intravenous (dose based on creatinine clearance)+Clindamycin intravenous 450–900 mg every 8 h+Ciprofloxacin intravenous 400 mg every 12 horMeropenem 500 mg every 8 h/cefotaxime 1–2 g every 8–12 h+Metronidazole 500 mg every 8 h/Clindamycin intravenous 450–900 mg every 8 hGAS Penicillin intravenous 1–2 million units every 6 h+Clindamycin intravenous 450–900 mg every 8 hS. aureus Nafcillin intravenous 1–2 g every 4–6 horOxacillin intravenous 1–1.5 g every 4–6 horCefazolin intravenous 1–2 g every 6–8 horClindamycin intravenous 450–900 mg every 8 hMRSA Vancomycin intravenous 1 g every 12 h (doses adjusted based on creatinine clearanceand vancomycin troughs)Clostridium Penicillin intravenous 1–2 million units every 6 h+Clindamycin intravenous 450–900 mg every 8 hP. aeruginosa Ceftazidime intravenous 2 g every 8 h
  3. 3. 212 Infectious Emergencies in Dermatologyfasciitis. Studies have showed varying success,and it should not replace the gold standard ofdebridement and antimicrobial therapy [7, 8].Mortality rates range from 20 to 40% [5]. Oneretrospective study identified eight independentpredictors of mortality for necrotizing fasciitis:liver cirrhosis, soft tissue air, Aeromonas infec-tion, a gram-negative facultative anaerobic rod,age over 60 years, band polymorphonuclear neu-trophils greater than 10%, activated partial thro-moplastin time of greater than 60 s, and serumcreatinine greater than 2 mg/dL [9].2.2.2 Preseptal and Orbital CellulitisBacterial infections involving the orbit poten-tially cause severe damage to the eye, cavernoussinus thrombosis, and death. Preseptal cellulitisis an infection of the eyelids and surroundingskin anterior to the orbital septum whereas orbitalcellulitis is an infection posterior to the septum.Preseptal cellulitis is usually secondary to traumaor bacteremia and the average age of patients is21 months of age. On the other hand, orbital (alsoknown as post-septal) cellulitis is a complicationof sinusitis, with average incident age of 12 years[10]. It is imperative to distinguish orbital celluli-tis from preseptal cellulitis as the former is amore severe infection, threatening permanentvision damage, requiring hospitalization, andintravenous antibiotics [3].Clinical signs can be useful in characterizingpreseptal and orbital cellulitis. Patients witheither form of cellulitis complain of pain, con-junctivitis, epiphora (insufficient tear film drain-age from the eyes), and blurred vision. Physicalexam will reveal periorbital erythema and edema.However, patients with orbital cellulitis may alsodisplay ophthalmoplegia, pain on eye motion,proptosis,visionloss,abnormalpapillaryreflexes,and/or disk edema [10]. If clinical evaluation isunequivocal, computed tomography (CT) withintravenous contrast can distinguish the two con-ditions [11].The pathogenesis of the infection usually dic-tates the causative organism. The pathogen inpreseptal cellulitis due to trauma is most likelyS. aureus or GAS, whereas preseptal cellulitisdue to primary bacteremia is usually due toStreptococcus pneumoniae. Orbital cellulitis maybe polymicrobial and is caused by pathogensresponsible for sinusitis, including S. pneumo-niae, non-typable Haemophilus influenzae,Moraxella catarrhalis, GAS, S. aureus, and/oranaerobes [10].Consultation with ophthalmology and otolar-yngology should be obtained immediately withconcomitant initiation of antimicrobials againstthe common pathogens. Preseptal cellulitis is man-aged with oral antibiotics whereas orbital cellulitisrequires intravenous antimicrobials. Surgical inter-vention, such as abscess drainage, has a role in themanagement of patients with orbital cellulitis. Arecent national perspective study found that olderpatients, those with diplopia, and hospital admis-sion via the emergency room were predictors ofsurgery [12]. With prompt initiation of antimi-crobials, prognosis is very good. When treatmentis inadequate or delayed, however, complicationsinclude blindness, cranial nerve palsies, brainabscesses, and death [13].2.2.3 Malignant Otitis ExternaMalignant otitis externa is a severe form of otitisexterna most commonly seen in elderly diabeticpatients. Patients often report failure of localtherapy. Clinically, they have severe tendernessaround the auricle, persistent drainage, and gran-ulation tissue at the junction of the osseous andcartilaginous portions of the external ear canal.Almost all cases are due to P. aeruginosa andantimicrobial treatment should be directed againstthis pathogen. While the treatment of choice waspreviously oral ciprofloxacin 750 mg twice dailywith or without rifampin, as mentioned previ-ously, increasing pseudomonal resistance tofluoroquinolones now necessitates hospitaliza-tion and intravenous antibiotics with a third-gen-eration cephalosporin, such as ceftazidime 2 gevery 8 h. Complications include osteomyelitisof the skull, nerve palsies, mastoiditis, sepsis,sigmoid sinus thrombosis, and a mortality rate ofaround 20% [5, 14].
  4. 4. 22 E. Stamell and K. Krishnamurthy2.2.4 MeningococcemiaMeningococcemia is a serious medical emer-gency that is frequently diagnosed by dermatolo-gists due to the presence of a classic petechialeruption seen in one-third to one-half of patients.The causative pathogen is Neisseria meningitidis,an aerobic Gram-negative diplococcus, and pri-marily affects young children and young adultswith a male predominance [15]. The incidence ofendemic disease is up to 5 cases per 100,000 pop-ulation per year worldwide [16]. Epidemic ratesof disease are seen in sub-Saharan Africa [17].The most common serogroups are A, B, C, Y, andW-135. Worldwide, the majority of cases are dueto serogroups A and C; however, in the UnitedStates, serogroups B and C predominate [15].Transmission is via respiratory droplets andthere is an average incubation period of 3–4 days[18]. Although not all N. meningitidis infectionsresult in septicemia, when they do, a petechialeruption precedes the development of ecchy-moses and ischemic necrosis (Fig. 2.1). Otheroccasional skin findings include bullous hemor-rhagic lesions and a transient blanchable morbil-liform eruption. The rash of meningococcemiacan be accompanied by systemic symptomsincluding fever, chills, hypotension, meningitis,meningoencephalitis, pneumonia, arthritis, peri-ardititis, myocarditits, and disseminated intravas-cular coagulation (DIC) [5].Prompt diagnosis and initiation of treatmentwith intravenous antibiotics are paramount.Diagnosis is confirmed through detection ofN. meningitidis in blood or cerebral spinal fluidcultures. Polymerase chain reaction analysis hasbeen developed for rapid detection of specificserogroups of N. meningitidis, but is not commer-cially available in many countries [18].Appropriate antibiotics include penicillin G500,000 U/kg/day in six divided doses, ceftriax-one 100 mg/kg/day in one or two divided doses,or cefotaxime 200 mg/kg/day in three divideddoses. Close contacts should receive prophylacticantibiotic treatment with rifampin [16, 19].Hearing loss, limb amputation, and a mortalityrate of 10% are among the complications ofmeningococcemia [20]. A quadrivalent polysac-charide vaccine has been available in the UnitedStates since 1982. This vaccine is effectiveagainst serogroups A, C, Y, and W-135 andinduces serotype-specific antibodies in olderchildren and adults, but is not immunogenic inyoung children. While this vaccine was approvedfor individuals older than 2 years of age, it wasonly recommended to control outbreaks, to pro-tect immunocompromised individuals, for peopletraveling to epidemic areas, or for individuals liv-ing in close quarters. Recommendations havemore recently changed with the development of aquadrivalent A, C, Y, and W-135 conjugate vac-cine. This vaccine provides long-term protectionas it induces immunologic memory [20]. Currentvaccination recommendations released by theCenters for Disease Control and Prevention(CDC) include routine vaccination of adolescentsat age 11–12 years, unvaccinated adolescents atentry to high school or age 15 (whichever comesfirst), all college freshman residing in dormito-ries, military personnel, and high-risk groups[16]. It is important to note that neither vaccineprotects against serogroup B, one of the mostcommonly isolated types in the United States.2.2.5 Rocky Mountain Spotted FeverRocky Mountain spotted fever (RMSF) is themost common rickettsial disease in the UnitedStates and is characterized by the history of a tickbite, fever, and rash [21]. Rickettsia rickettsii, asmall gram-negative bacteria, is transmitted intothe dermis by a tick bite and replicates in theFig. 2.1 Meningococcemia
  5. 5. 232 Infectious Emergencies in Dermatologyendothelial cells, subsequently causing vasculi-tis, hypoperfusion, and end-organ damage. In theUnited States, the vector is the American dogtick, Dermacentor variabilis, and the RockyMountain wood tick, Dermacentor andersoni[22]. RMSF has been reported in the UnitedStates, Western Canada, Western and CentralMexico, Panama, Costa Rica, NorthwesternArgentina, Brazil, and Colombia. In the UnitedStates, RMSF has occurred in every state exceptfor Vermont and Maine, with half the cases foundin Oklahoma, Tennessee, Arkansas, Maryland,Virginia, and the Carolinas [23]. Up to 1,200cases annually have been reported in the UnitedStates, but there are likely a number of unreportedcases each year [24]. The highest incidence ofdisease has been seen in children less than 10years of age and adults between 40 and 64 yearsold as well as men and Caucasians [23].The diagnosis is primarily clinical. The triadof fever, headache, and rash in an individual withthe history of a tick bite or exposure to ticksshould raise suspicion for RMSF; however, this isonly seen in 3% of patients with RMSF [25].Fever often accompanied by headache and myal-gia precedes the rash by 3–6 days. Other earlysymptoms include nausea, vomiting, and abdom-inal pain. The patient may eventually develophypotension, thrombocytopenia, and acute renalfailure followed by hypotensive shock and acuterespiratory failure. The rash begins as small mac-ules around the wrists and ankles, eventuallyinvolving the majority of the body, but spares theface. Red-pink macules and papules are seen onthe palms and soles later in the course of disease.Petechiae develop within the macules or papulesdue to severe vascular injury. The petechiae even-tually evolve to cutaneous necrosis [5, 19, 21].Definitive diagnosis can be made byimmunofluorescence or immunohistochemistry ina biopsy specimen of an eschar, macule, papule,or petechial lesion. Serologic diagnosis cannot beutilized at the time of diagnosis as antibodies do notdevelop until at least 7 days after the onset of theillness.Acute and convalescent-phase serum sam-ples can be used for indirect immunofluorescence,latex agglutination, and enzyme immunoassay todetect anti-rickettsial antibodies. Often a clinicaldiagnosis is rendered as treatment with doxycy-cline 100 mg twice daily for adults or 2.2 mg/kgtwice daily for children under 45 kg for 7–14 daysshould not be delayed for diagnostic confirmation[21]. Chloramphenicol 50 mg/kg is an alternativetreatment for patients younger than 9 years of ageor pregnant women [18]. Of 100 individualsinfected, 5–10 of those will die and many otherswill suffer amputation, deafness, or permanentlearning disability from hypoperfusion [22]. Asthere are no current vaccines to prevent rickettsialdiseases, preventative measures have been empha-sized. General recommendations for preventionof RMSF include avoidance of tick habitats,implementation of personal protective measuresto limit possibility of tick exposure, frequentexamination of oneself to identify any attachedticks, and proper removal of attached ticks toreduce transmission [23, 26]. A minimum of4–6-h period of attachment is required fortransmission of R. rickettsii. Therefore, early andproper removal techniques are emphasized todecrease the risk of transmission. These includewearing protective gloves, grasping the tick withfine forceps close to the point of attachment andpulling straight outward, avoiding jerking, twist-ing, or squeezing the tick, and disinfecting thebite wound after tick removal [27]. Both the useof Tick repellent (N,N-diethyl-meta-toluamide,DEET) on exposed skin and application of an aca-ricide (e.g.,disease is caused permethrin) on cloth-ing can be helpful [23, 28].2.2.6 Lyme DiseaseLyme disease, also known as Lyme borreliosis, isthe most common tick-borne infectious diseasein North America [29]. The disease is caused bythe spirochete Borrelia burgdorferi sensu latocomplex and is transmitted by Ixodes ticks. In theUnited States, Lyme borreliosis is causedspecifically by B. burgdorferi sensu stricto andIxodes scapularis serves as the primary vector.Small mammals, such as white-footed mouse,white-tailed deer, and raccoons, and are the reser-voir for the disease. Lyme disease is transmittedthrough the saliva of the Ixodes ticks, and a
  6. 6. 24 E. Stamell and K. Krishnamurthyfeeding period of more than 36 h is usuallyrequired for transmission [30]. Disease transmissionis most common between June and August [29].Erythema migrans is the most common clini-cal manifestation of localized disease and hasbeen seen in as many as 89% of patients in onecase series [31]. Clinically, an expanding redannular patch with or without central clearing isappreciated at the site of the tick bite. Borreliallymphocytoma, a painless bluish-red nodule orplaque usually on the ear lobe, ear helix, nipple,or scrotum, is a rare cutaneous lesion that alsooccurs at the site of a tick bite during the earlydisseminated stage of Lyme disease. Early dis-seminated disease is characterized by one of thefollowing: two or more erythema migrans lesions,Lyme neuroborreliosis (meningo-radiculitis,meningitis, or peripheral facial palsy), or Lymecarditis (acute onset of atrioventricular conduc-tion delays, rhythm disturbances, myocarditis, orpericarditis). Late Lyme disease manifests asarthritis, which is characterized by recurrentattacks or persistent swelling in one or more largejoints, or acrodermatitis chronica atrophicans(chronic erythematous plaques on the extensorsurfaces of the extremities, which eventuallybecome atrophic) [32]. Late Lyme neuroborrelio-sis is uncommon and presents as slowly progress-ing encephalomyelitis [33].Diagnosis of Lyme disease can be made clini-cally by the presence of erythema migrans asserologic studies early in the disease are gener-ally negative [29]. Serologic evaluation is pur-sued in patients without erythema migrans.Samples are first screened with an enzyme-linkedimmunosorbent assay (ELISA). IgM antibodiesappear 2–6 weeks after exposure and IgG titerscan be detected 3–4 weeks thereafter [34]. Theutility of the ELISA varies depending on diseaseprevalence. The positive predictive value is muchlower, ranging from 8 to 28% depending on thesensitivity and specificity, in a region with lowprevalence of disease whereas the positive pre-dictive value is as high as 83% in a region with ahigh prevalence of disease. The false negativerate is low for the ELISA with the negative pre-dictive value of the test ranging from 95 to 99%[35]. If the ELISA is positive or equivocal, thenIgM and IgG immunoblots are performed. Ofnote, IgG levels are positive after at least 4 weeksof symptoms [36].Treatment is required to prevent disseminateddisease and the development of delayed compli-cations. A single dose of doxycycline 200 mgorally can be administered within 72 h of removalof an Ixodes scapularis as a chemoprophylacticmeasure except to children less than 8 years ofage and pregnant women [39]. Doxycycline100 mg twice daily and amoxicillin 500 mg twicedaily are both indicated in the treatment of Lymedisease. Cefuroxime axetil 500 mg twice daily isconsidered second line due to cost and intrave-nous penicillin is now limited to cases with neu-rologic involvement. The length of treatmentvaries based on the clinical manifestations of thedisease. A 14-day course of antibiotics is indi-cated in patients with neurologic involvement orborrelial lymphocytoma. A 28-day course ofantibiotics, on the other hand, is required inpatients with late neuroborreliosis, recurrentarthritis after one course of oral treatment, andacrodermatitis chronica atrophicans [29, 37].Prevention of infection is vital in decreasingthe incidence of infections and the developmentof late complications. Repellents are the mosteffective modality to prevent tick attachment, andthe most frequent agent used is DEET [38].Repellents combined with protective clothinghave been shown to reduce the incidence of Lymedisease infections [40]. Permethrin can be appliedto clothing, shoes, bed nets, or other outdoorequipment, but has limited utility as a topicalagent [38]. If a tick is found attached to an indi-vidual, care should be taken to remove the tickappropriately.BoththeWorldHealthOrganizationand the CDC recommend using fine-tipped for-ceps to grasp the tick closest to the point of entryto the skin, and the body of the tick should not becompressed [34].2.2.7 AnthraxAnthrax is caused by Bacillus anthracis, an aerobicGram-positive rod, and results in three differentclinical syndromes depending on the mode of
  7. 7. 252 Infectious Emergencies in Dermatologytransmission: cutaneous anthrax via inoculation,pulmonary anthrax via inhalation, and gastroin-testinal anthrax via ingestion. B. anthracis pro-duces three polypeptides that comprise anthraxtoxin: protective antigen (PA), lethal factor (LF, aprotease), and edema factor (EF, an adenylcyclase). The PA binds to cellular receptors, iscleaved by cellular furin, oligomerizes, and trans-ports LF and EF into cells. Edema toxin (ET, thecombination of PA and EF) is a calcium- andcalmodulin-dependent adenylate cyclase thatincreases the intracellular level of cyclic AMP(cAMP), and ultimately leads to impaired waterhomeostasis and cellular edema. Lethal toxin(LT, the combination of PA and LF) is a zinc-dependentendoprotease.ItcleavestheN-terminusof mitogen-activated protein kinase kinases(MAPKK) and thus inhibits the MAPKKs.As such,lethal toxin promotes macrophage apoptosis andrelease of tumor necrosis factor alpha (TNF-a)and interleukin-1 beta (IL-1b) [41]. ET and LTare responsible for the clinical symptoms ofanthrax infection.In cutaneous anthrax, the most common form,spores gain access to the skin via trauma and ger-minate within macrophages locally. The result isedema and necrosis from toxins and ahyperinflammatory response. Although themajority of cases remain localized, up to 10% ofuntreated cutaneous anthrax may disseminate. Inthis situation, macrophages carry the spores toregional lymph nodes where they germinate andthe bacteria rapidly multiply. It subsequently dis-seminates through the blood, causing hemor-rhagic lymphadenitis and possible death fromsepticemia and toxemia [42].Cutaneous anthrax starts as a painless pru-ritic papule approximately 1–12 days after inoc-ulation. The papule enlarges and develops acentral vesicle or bulla with surrounding edemawithin 48 h. The vesicle becomes hemorrhagicwith the subsequent development of necrosisand ulceration. The classic black eschar (thickcrust) develops over the ulcer with edema anderythema remaining a prominent feature [43].Associated symptoms include fever, headache,malaise, and regional lymphadenopathy [44]. In90% of cases, the eschar disengages and healswithout scarring over 1–2 weeks withoutsystemic complications. However, in the other10% of cases, edema of the head and neck result-ing in respiratory compromise or toxic shockfrom overwhelming septicemia can occur [45].Diagnosis of anthrax must be confirmed withserology or polymerase chain reaction assay viathe CDC; however, these tests can take severaldays. Treatment should not be delayed forconfirmation. In uncomplicated cases of cutaneousanthrax, oral ciprofloxacin 500 mg twice daily ordoxycycline 100 mg twice daily is indicated foradults. For children, oral ciprofloxacin 10–15 mg/kg twice daily, not to exceed 1 g/d, or doxycycline100 mg twice daily should be used. The CDCcurrently advocates for a 60-day course of antibi-otics given increased likelihood of reexposure.Intravenous ciprofloxacin 400 mg every 12 h ordoxycycline 100 mg every 12 h are indicated forcomplicated cases of cutaneous anthrax [3]. Themortality rate in untreated cutaneous anthrax isas high as 20%. However, with appropriate treat-ment, the mortality rate is less than 1% [46].2.2.8 TularemiaTularemia, a bacterial infection caused byFrancisella tularenis, a Gram-negative, nonmo-tile coccobacillus, can present as six distinct syn-dromes according to the mode of transmissionand clinical presentation: ulceroglandular, glan-dular, oculoglandular, oropharyngeal/gastroin-testinal, typhoidal/septicemic, and pneumonic[5]. Tularemia is an arthropod-borne disease andis transmitted by the ticks, Amblyomma america-num (lone-start tick), Dermacenter andersoni(Rocky Mountain wood tick), and Dermacentervariabilis (American dog tick) as well as thedeerfly, Chrysops discalis. F. tularensis can alsobe transmitted by handling infected mammals,such as rabbits, muskrats, prairie dogs, and otherrodents, or by contaminated food or water [47].Ulceroglandular tularemia is the most com-mon type and accounts for 80% of cases of tula-remia. A painful erythematous papule developsat the inoculation site and can be solitary or mul-tiple depending on the mode of transmission. Thepapule(s) develop first into a pustule and then apunched-out ulcer with raised ragged edges and a
  8. 8. 26 E. Stamell and K. Krishnamurthygray-to-red necrotic base [48]. A necrotic escharis seen at the site of the ulcer and tender regionallymphadenopathy follows. In contrast to cutane-ous anthrax, the eschar heals with scarring afterseveral weeks to months [48]. Sudden onset offlu-like symptoms develops on average 4–5 daysafter inoculation. Hematogenous spread to thespleen, liver, lungs, kidneys, intestine, centralnervous system, and skeletal muscles can occur[47]. Tularemids, or secondary eruptions, mayoccur following hematogenous disseminationand presents as macular, morbilliform, nodular,acneiform, papulovesicular, or plaque-like erup-tions [48].Oculoglandular tularemia occurs in less than1% of cases of tularemia and can present withconjunctivitis, periorbital edema and erythema,lymphadenopathy, and lymphadenitis [49]. Theother forms of tularemia do not present with cuta-neous findings.Diagnosis is made by fluorescent antibodytesting. First-line treatment is streptomycin 1 gintramuscularly every 12 h for 10 days, but intra-venous gentamicin 1.5–2 mg/kg loading dose fol-lowed by 1–1.7 mg/kg every 8 h or 5–7 mg/kgevery 24 h, ciprofloxacin 500–750 mg twice aday for 10 days, or levofloxacin 500 mg daily for14 days have also proven efficacious in the treat-ment of tularemia. Doxycycline 100 mg oral orintravenous for 14–21 days has also demonstratedefficacy, but is associated with higher risk ofrelapse [5, 50].2.2.9 Staphyloccocal Scalded SkinSyndromeStaphylococcal scalded skin syndrome (SSSS),also known as Ritter’s disease or pemphigusneonatorum, is caused by S. aureus exfoliative(also known as epidermolytic) toxins (ETs), pri-marily A and B. The toxins are directed againstdesmoglein-1, a desmosomal adhesion molecule,which causes an intraepidermal split through thegranular layer [51]. As a toxin-mediated disease,the bacterial infection usually lies at a distantfocus,mostcommonlytheconjunctiva,nasophar-ynx, ear, urinary tract, or skin, and no organismis recovered from lesional skin, yielding nega-tive tissue cultures [18]. SSSS primarily affectschildren and rarely adults with renal disease, asthe exfoliative toxins are excreted by the kid-neys, or immunocompromise [19, 52, 53].The initial signs of SSSS are abrupt onset offever, skin tenderness, and toxic erythema. Theerythema first appears on the head and general-izes in 48 h, but sparing the palms, sole, andmucous membranes. Flaccid bullae may develop,and the Nikolsky sign is positive [19]. Within 1–2days, the skin sloughs, usually starting in theflexural areas. Scaling and desquamation occurfor the next 3–5 days, and re-epithelialization isseen 10–14 days after the initial signs [5](Fig. 2.2). Of note, the absence of mucosalinvolvement is helpful in clinical differentiationof SSSS from Stevens–Johnson Syndrome andFig. 2.2 Ritter’s disease
  9. 9. 272 Infectious Emergencies in Dermatologytoxic epidermal necrolysis (TEN), as desmog-lein-1 is not expressed in mucosal epithelium. Inaddition, the diagnosis can be distinguished fromTEN by histologic examination of the roof of ablister, as TEN shows full thickness epidermalnecrosis, whereas SSSS only affects the upperlayers of the epidermis.Both immediate initiation of appropriateantimicrobials and supportive care are crucial[19]. Antimicrobial regimens for SSSS includedicloxacillin 2 g every 6 h or cefazolin 1 g every8 h. If MRSA is suspected, then vancomycin1 g every 12 h, with doses adjusted based oncreatinine clearance and vancomycin troughs,is indicated [54]. Prognosis is good in children,but mortality in adults approaches 50%. Inadults with underlying disease, mortality isalmost 100% [55].2.2.10 Toxic Shock SyndromeToxic shock syndrome (TSS) results from therelease of bacterial antigens, known as superanti-gens, from S. aureus, GAS, and group C strepto-coccus. The superantigen causes leakingcapillaries, which clinically results in fever, exan-them, mucositis, “strawberry” tongue, hypoten-sion, multiorgan dysfunction, and convalescentdesquamation [56]. Superantigens have the abil-ity to bypass MHC-limited antigen processing,and instead bind unprocessed directly to MHCclass II molecules and activate T-cells [57].TSS can be divided into two categories: men-strual and non-menstrual. Menstrual TSS is sec-ondary to strains of S. aureus that produce toxicshock syndrome toxin-1 (TSST-1) and histori-cally has been linked to superabsorbent tampons[58]. Non-menstrual TSS is associated with anystaphylococcal infection that produces TSST-1,staphylococcal enterotoxin (SE) serotype B, andSE serotype C in addition to 11 different strepto-coccal superantigens [59, 60].Staphylococcal TSS has an abrupt onsetwith flu-like symptoms followed by confusion,lethargy, and agitation. Rash is common earlyin the illness; however, the characteristicdesquamation does not occur until 10–21 daysafter the onset of disease [54]. In contrast, thedesquamation in TEN is full thickness andoccurs hours to days from the first signs of thedisease [5]. The source of infection in staphylo-coccalTSS is not always clear and is not identifiedin a large number of patients. S. aureus is rarelycultured from the blood, but instead is found inthe focus of infection if one is identified. Incontrast to staphylococcal TSS, which occursin the setting of menstruation or nosocomialinfections, streptococcal TSS usually arisesfrom deep invasive soft-tissue infections [57].The illness is similar, although more than 60%of cases have positive blood cultures and thesource of infection is usually easy to identify[57, 61]. In addition, mortality rate is muchhigher in streptococcal TSS [62].Supportive management, source control, andappropriate antimicrobial coverage are the mostimportant immediate steps in treatment. However,it is important to recognize that treatment mustboth reduce organism load and exotoxin produc-tion [57]. Antimicrobial regimens are tailored tothe specific organisms responsible for TSS.Table 2.2 outlines first- and second-line therapiesfor GAS, MSSA, and MRSA infections(Table 2.2). It is important to mention that therole of clindamycin or linezolid in the antimicro-bial regimen is to inhibit toxin production by bothS. aureus and GAS [57].IVIG has been used as an adjuvant therapy inthe treatment of TSS as it has been shown toblock T-cell activation by staphylococcal andstreptococcal superantigens [63]. A Canadiancomparative observational study found that therewas an improved 30-day survival in 21 patientswho received IVIG compared to the 32 patentswho did not [7]. Subsequently, a multicenter ran-domized placebo control trial attempted to exam-ine the efficacy of IVIG in streptococcal TSS;however, the trial only enrolled 21 patients andwas terminated due to low recruitment. The studydid analyze the 21 patients and found that therewas a higher mortality rate in the placebo groupat 28 days, although it did not meet statisticalsignificance [8].
  10. 10. 28 E. Stamell and K. KrishnamurthyFig. 2.3 Purpura fulminans2.2.11 Purpura FulminansPurpura fulminans is seen in three clinical set-tings: hereditary deficiency of protein C or S;acute infectious purpura fulminans; and idio-pathic purpura fulminans [64]. The acute infec-tious purpura fulminans is the most commonform and is discussed in this section [19]. A num-ber of infections induce this syndrome, but thetwo most common are Neisseria meningitidis andstreptococcal infections [65].Infectious purpura fulminans begins with der-mal discomfort that progresses within hours topetechiae that then coalesce to form purple ecchy-moses [66] (Fig. 2.3). The ecchymoses evolveinto hemorrhagic bullae with subsequent necrosisand gangrene [67]. The affected areas are initiallysterile, but can develop secondary infections. Thepathology in purpura fulminans is not limited tothe skin, and as a result, there can be multiorganfailure [68]. Other associated findings includefever, DIC, and flu-like symptoms [67].If recognized at the initial stage prior to devel-opment of necrosis, the syndrome may be com-pletely reversed [67]. The primary treatment issupportive in conjunction with appropriate anti-microbials to treat the underlying infection.Vasopressors may actually contribute to poorperipheral circulation and peripheral tissue dam-age and should be avoided [19, 67].2.2.12 Ecthyma GangrenosumEcthyma gangrenosum is an uncommon cutane-ous variant of impetigo most commonly associatedwith P. aeruginosa septicemia, but may occurwithout bacteremia. It occurs in up to 2.8% ofpatients with P. aeruginosa bacteremia. The mor-tality rate in individuals with ecthyma gangrenosumdue to Pseudomonas septicemia can approach77% compared to the 15% mortality rate in thosewithout bacteremia [69]. The most common riskfactor is neutropenia usually due to underlyingTable 2.2 Antimicrobial regimens for TSS [3, 57]Organism First-line therapy Second-line therapyGAS Penicillin G 3–4 million units every 4 h+Clindamycin 600–900 mg every 8 hMacrolide or fluorquinolone+Clindamycin 600–900 mg every 8 hS. aureus (MSSA) Cloxacillin 500 mg PO every 6 horNafcillin 1–2 g IV every 4–6 horCefazolin 500–1,000 mg every 6–8 h+Clindamycin 600–900 mg every 8 hClarithromycin 250–500 mg PO+Clindamycin 600–900 mg every 8 hS. aureas (MRSA) Vancomycin 1 g every 12 h (adjusted for creatinineclearance)+Clindamycin 600–900 mg every 8 horLinezolid 600 mg IV/PO every 12 h
  11. 11. 292 Infectious Emergencies in Dermatologymalignancy or immunosuppressive therapy.Ecthyma gangrenosum may occur more fre-quently in infections associated with primaryimmunodeficiencies, including hypogammaglob-ulinemia, dysfunctional neutrophils, and chronicgranulomatous disease [69, 70]. Occasionally,ecthyma gangrenosum may occur in healthy indi-viduals without any predisposing factors; how-ever, underlying risk factors should be sought out[69, 71].Ecthyma is a vasculitis affecting the mediaand adventitia of blood vessels due to hematoge-nous spread of a pathogen or direct inoculationvia the skin [69]. The eruption begins as ery-thematous or purpuric macules usually in theanogenital area or on an extremity. The lesionsevolve into hemorrhagic vesicles or bullae whichrupture to form a gangrenous ulcer with a centralgray-black eschar [72]. The lesions develop over12 h and may exist in different stages on the sameindividual [69]. On histology, lesions show necro-tizing hemorrhagic vasculitis, and Gram-negativerods may be visible in the medial and adventitialwalls of deeper vessels [72].In addition to blood and urine cultures, biopsyof a lesion for tissue culture should be performedwith immediate administration of anti-pseudomonal antimicrobials [73]. Due topseudomonal resistance, intravenous antibioticswith a third-generation cephalosporin with anti-pseudomonas activity, such as ceftazidime 2 gevery 8 h, are indicated.2.3 Viral Infections2.3.1 Herpes Simplex VirusHerpes simplex virus (HSV) is generally associ-ated with self-limiting infections. However, thereare a few circumstances where HSV is adermatological emergency and those clinical sce-narios are covered in this section: neonatal HSV,in the setting of immunosuppression, and eczemaherpeticum. The mainstay of treatment of HSV inemergency situations is intravenous acyclovir.Neonatal HSV occurs in approximately 1 in3,200 deliveries [74]. HSV may be transmitted tothe neonate during the intrauterine (5%),intrapartum (85%), or postpartum (10%) periods[3]. In comparison with primary genital herpes,recurrent genital herpes is more common duringpregnancy. However, women with primary geni-tal HSV disease are at the highest risk of trans-mitting HSV to the baby [75]. Approximatelytwo-thirds of women who acquire genital herpesduring pregnancy are asymptomatic, and inaccordance with this number, 60–80% of womenwho deliver an HSV-infected infant have no evi-dence of genital HSV at delivery [76, 77]. Infantswho acquire HSV in utero typically have a triadof cutaneous manifestations, ophthalmologicfindings, and neurologic involvement. Cutaneousmanifestations include scarring, active vesicularlesions, hypo- and hyperpigmentation, aplasiacutis, and an erythematous macular exanthem[75]. HSV can manifest as three different types ofinfections in neonates: involvement limited to theskin, eyes, or mouth, central nervous system, anddisseminated multiorgan infections [3].Disseminated disease occurs in approximately25% of neonatal HSV infections with approxi-mately 80% of these cases presenting with avesicular eruption [78]. Complications includeencephalitis in 60–75% of cases, severe coagul-opathy, liver dysfunction, pulmonary involvement,and a high mortality rate [75, 79]. Neonatal HSVinfection should be treated with intravenous acy-clovir 10–20 mg/kg every 8 h for 10–21 days.Immunosuppressed patients are at risk ofdeveloping fulminant herpes infections. Vesiclesenlarge to form hemorrhagic blisters and deepulcers [80] (Fig. 2.4). Death is often secondaryto visceral involvement and despite early treat-ment with intravenous acyclovir 10 mg/kg idealbody weight every 8 h for 7–14 days, herpesencephalitis carries significant morbidity andmortality [81].Eczema herpeticum (also known as Kaposi’svaricelliform eruption) is a herpetic superinfec-tion of a preexisting skin disease, such as atopicdermatitis, cutaneous burns, or skin compromisesustained during cosmetic procedures. Clinically,there is an acute onset of monomorphic vesiclesand pustules that coalesce into large superficialerosions that are susceptible to superinfection
  12. 12. 30 E. Stamell and K. Krishnamurthy[82] (Fig. 2.5). Patients may experience constitu-tional symptoms. In eczema herpeticum, herpeticlesions bypass the nerve endings and ganglionsand directly spread to a diseased cutaneous region[83]. Rapid initiation of intravenous acyclovir5–10 mg/kg ideal body weight every 8 h for 5–7days is crucial as HSV may completely dissemi-nate and lead to possible death [84].2.3.2 Varicella Zoster Virus2.4 VaricellaVaricella zoster virus (VZV) presents as varicella(chickenpox) as a primary infection and herpeszoster (shingles) when the virus is reactivated.Clinically, varicella lesions start as small ery-thematous papules, which evolve into vesicles onan erythematous base resembling “dew drops ona rose petal” (Fig. 2.6). The vesicles quicklyevolve into pustules that form a crust. The lesionsmay occur in crops, and the presence of lesions invarious stages of development is a characteristicof this condition. Mucosal surfaces may developaphthous-like ulcers [80]. Both varicella and her-pes zoster are usually self-limited diseases, butsimilar to HSV infection, there are specific cir-cumstances where VZV infections are dermato-logical emergencies.Neonatal varicella is seen in two clinical set-tings: primary VZV infection during pregnancythat is transmitted across the placenta or primaryVZV infection during the perinatal period. Theformer can occur at any point during gestation andresults in either congenital varicella syndromeand/or fetal death. It is worth mentioning that notall primary VZV infections during pregnancyresult in transplacental infection. Congenital vari-cella syndrome most commonly occurs withtransplacental VZV infection between 13 and 20weeks of gestation [85]. Affected babies developcicatricial skin lesions that may be depressed andhyper- or hypopigmented in a dermatomal distri-bution. Other affected organ systems include ocular(chorioretinitis, microphthalmia, nystagmus, andHorner’s syndrome, which is the triad of miosis,ptosis, and anhidrosis), musculoskeletal (hypoplasiaFig. 2.6 Varicella virusFig. 2.4 Herpes simplex virusFig. 2.5 Kaposi varicelliform eruption
  13. 13. 312 Infectious Emergencies in Dermatologyof bones and muscles and malformed digits), centralnervous system (cortical atrophy, seizures, mentalretardation, and microcephaly), and autonomicnervous system (neurogenic bladder, hydroureter,esophageal dilation, and reflux). Prognosis is poorand death during infancy results from gastroe-sophageal reflux, aspiration pneumonia, orrespiratory failure [86].The second form of neonatal varicella is peri-natal varicella, which occurs when there ismaternal disease 5 days before delivery to 2 daysafter delivery. Infants develop the classic skinvesicles on an erythematous base; however, dis-semination may result in pneumonia, hepatitis,encephalitis, and severe coagulopathy [86].Infants exposed to maternal infection should begiven VZIG if available or IVIG at birth or assoon as maternal symptoms develop [87]. DespiteVZIG or IVIG, varicella can still develop andacyclovir should be administered if there are anysigns of illness [86].Varicella infections can be life-threatening ina few other circumstances. Immunocompromisedindividuals with varicella or herpes zoster havean increased risk for systemic complicationsincluding pneumonitis, central nervous systeminvolvement, pneumonia, thrombocytopenia, andliver function impairment [80]. Although lessthan 5% of varicella cases occur in immunocom-petent adults, 55% of deaths due to varicellaoccur in adults. Adults with varicella infectionare at increased risk of pneumonitis and mostcommonly expire secondary to pneumonia withrespiratory failure [88].A live attenuated varicella vaccine wasapproved for use in children in the United Statesin 1995 [89]. The vaccine is indicated for chil-dren 12 months to 12 years of age in addition toindividuals greater than 13 years old who have noevidence of immunity. Finally, the vaccine shouldbe offered to high-risk adults without immunity,including health care providers, household contactsof immunocompromised individuals, nonpreg-nant women of childbearing age, individuals whowork in places where chickenpox transmissionmay occur, and international travelers [90]. It isnoteworthy that the varicella vaccine may reducethe incidence and severity of herpes zoster [5].2.5 Herpes ZosterHerpes zoster, the latent reactivation of previousVZV, is rarely life-threatening; however, dissem-inated disease can be associated with increasedmorbidity and mortality [80]. Herpes zosterinfection is heralded by paresthesias or stabbingpain. Shortly thereafter, an eruption of small ves-icles in the same distribution as the pain appearsand crusts over during the next 15 days [80](Fig. 2.7). Generally, herpes zoster appears in adermatomal distribution; however, in immuno-suppressed patients, disseminated disease mayoccur, defined as more than 20 vesicles outsidethe area of the primary or adjacent dermatome[5]. Common complications of disseminated dis-ease include pneumonia, encephalitis, and hepa-titis. The mortality rate has been reduced due toantiviral therapy.Herpes zoster often begins with a prodrome ofintense pain associated with pruritus, tingling, orhyperesthesia. If severe enough, the pain can bemisdiagnosed as an acute abdomen or myocar-dial infarction, depending on the dermatomeinvolved. Patients usually present with tinglingand paresthesia in the dermatome where cutane-ous lesions eventually develop. Diagnosis is oftendelayed as the cutaneous lesions are not presentat the onset of disease and mortality rate remainshigh despite initiation of antiviral therapy [91].Immunocompromised patients are at anincreased risk not only for uncomplicated herpeszoster infections but also for complications ofFig. 2.7 Zoster virus
  14. 14. 32 E. Stamell and K. Krishnamurthyzoster. Patients with AIDS or other conditionswith depressed cellular immunity are at risk forchronic VZV encephalitis which may occurmonths after an episode of herpes zoster. Patientshave a subacute clinical presentation with head-ache, fever, mental status changes, seizures, andfocal neurologic defects [91]. Cerebrospinal fluidanalysis reveals VZV DNA by polymerase chainreaction [92]. Death often results, although casereports have shown that high-dose intravenousacyclovir therapy may be efficacious [91].Ramsay Hunt syndrome, also known as herpeszoster oticus, is a herpetic infection of the inner,middle, and external ear. It is a reactivation oflatent VZV virus in the geniculate ganglion, thesensory ganglion of the facial nerve; however,reactivation affects both the facial nerve (cranialnerve VII) and the vestibulocochlear nerve (cra-nial nerve VIII) due to their close proximity [93].The incidence is about 5 cases per 100,000 of theUS population annually and occurs more fre-quently in individuals over the age of 60 years[94]. Patients present with severe ear pain, smallvesicles on the pinna or oral mucosa, and facialpalsy [95]. Prompt diagnosis is paramount as ini-tiation of antiviral therapy within 72 h of theonset of symptoms leads to resolution of thefacial palsy in as many as 75% of cases [94].Herpes zoster ophthalmicus, the second mostcommon presentation of herpes zoster, involvesthe ophthalmic division of the trigeminal nerveand occurs in up to 20% of patients with herpeszoster [96, 97]. The ophthalmic division dividesintothenasociliary,frontal,andlacrimalbranches.The nasociliary nerve innervates the anterior andposterior ethmoidal sinuses, conjunctiva, sclera,cornea, iris, choroid, and the skin of the eyelidsand tip of the nose [96]. Hutchinson’s sign, firstdescribed in 1864, is the appearance of a herpeszoster lesion on the tip or side of the nose andserves as a useful prognostic factor in the ensuingocular inflammation [98]. Uveitis followed bykeratitis are the most common forms of ocularinvolvement [19]. Clinically, patients developlesions on the margin of the eyelid occasionallyassociated with periorbital edema and ptosis.Chronic disease due to neurologic damage occursin up to 30% of patients with this form of herpeszoster [99]. Early complications include residualptosis, lid scarring, deep scalp pitting, entropion,ectropion, pigmentary changes, and lid necrosis[97]. Glaucoma, optic neuritis, encephalitis,hemiplegia, and acute retinal necrosis are moresevere long-term complications, the risk of whichmay be reduced by half with prompt initiation ofantiviral therapy [19]. If herpes zoster ophthal-micus is suspected, ophthalmology should beconsulted immediately.While uncomplicated zoster may be adequatelytreated with oral antivirals, such as valacyclovir1 g every 8 h for 7 days, disseminated and severeinfections require intravenous acyclovir 10 mg/kgideal body weight every 8 h for 7–14 days.Although corticosteroids may be added as anadjuvant therapy in herpes zoster infections due totheir anti-inflammatory properties, studies havefailed to show a beneficial effect on acute pain andin some instances had adverse effects, includinggastrointestinal symptoms, edema, and granulo-cytosis. However, in Ramsay Hunt syndrome,steroids may be added to antiviral therapy ifthere are no contraindications [100].Zostavax is a live attenuated vaccine indicatedfor the prevention of herpes zoster and post-her-petic neuralgia in individuals greater than 50years of age [101]. The vaccine has been shownto reduce the incidence of herpes zoster by 51%,reduce the incidence of post-herpetic neuralgiaby 67%, and reduce the herpes zoster-related bur-den of illness by 61% [102]. Gabapentin has beenapproved since 2002 by the US Food and DrugAdministration (FDA) for the treatment of post-herpetic neuralgia [103].2.5.1 CytomegalovirusCytomegalovirus (CMV) or human herpesvirus-5(HHV-5), a large double-stranded DNA virus ofthe viral family herpesviruses, is acquired by expo-sure to infected children, sexual transmission, andtransfusion of CMV-infected blood products. Upto 80% of adults are infected with CMV [19].CMV causes a mild form of infectious mononu-cleosis in most affected immunocompetent indi-viduals; however, in rare cases, fatal massive
  15. 15. 332 Infectious Emergencies in Dermatologyhepatic necrosis can occur. Immunocompromisedindividuals, including those with HIV, malignancy,or post-organ transplant patients, may have severe,complicated CMV infections [3].CMV infection in immunocompromised indi-viduals can either directly induce death or disablethe patient’s immune system, making them evenmore susceptible to secondary infections [104].CMV can be a fatal disease in newborns. When aprimary CMV infection is sustained during preg-nancy, transplacental transmission may occur andseverely affect the fetus [80]. Nonimmune preg-nant women, especially those working in health-care settings or daycare facilities, should takeprecautions, primarily proper hand washing.Cutaneous manifestations of congenital CMVinclude jaundice, petechiae, and purpura, referredto as “blueberry muffin” lesions and complicationsinclude hearing loss and mental retardation [3].Antiviral therapy should be given to affectedimmunocompromised patients in addition to pas-sive immunization of CMV with hyperimmuneglobulin (HIG). Women who develop primaryCMV infections during pregnancy may preventtransmission to the fetus with CMV HIG.Ganciclovir is not approved for pregnant women,but is safe for newborns [3].2.5.2 Measles (Rubeola)Measles, due to the morbillivirus, an RNA virusin the Paramyxoviridae family, has markedlydecreased in incidence since the development ofvaccination against the virus. However, it remainsan active disease in both developed and develop-ing countries [105]. Generally, affected individu-als are unvaccinated children less than 5 years ofage or vaccinated school-age children who failedto develop immunity to the vaccine [106].The virus is transmitted via respiratory secre-tions. Following an asymptomatic incubation of10–11 days, a high fever develops with subse-quent rapid defervescence. Coryza, conjuncti-vitis, and a barking cough are characteristic.Additionally, an eruption begins on the head witherythematous macules and papules that coalesceand spread distally involving the palms and soles.One to two days prior to the exanthem, Herman’sspots, bluish gray areas on the tonsils, andKoplik’s spots, punctate blue-white lesionssurrounded by an erythematous ring on the buc-cal mucosa, appear [80]. Complications of mea-sles include encephalitis, subacute sclerosingpanencephalitis, and fetal death if infectionoccurs during pregnancy [107].Vaccination is the gold standard for prevent-ing infection. The measles, mumps, rubella(MMR) or MMR plus varicella (MMRV) is a liveattenuated vaccine and as a result cannot be usedin immuncompromised patients [3]. Although noantivirals have been effective in treating measlesinfection, vitamin A supplementation may reducedeaths from measles by 50% as vitamin Adeficiency has been shown to increase morbidityand mortality [108].2.5.3 German Measles (Rubella)Rubella is a viral infection caused by the rubellavirus, an RNA virus in the Togaviridae family. Itis associated with mild constitutional symptomsthat are more severe in adults compared to chil-dren. Following a 2-week incubation period, apale erythematous eruption appears on the headand spreads to the feet, lasting approximately 3days. Forchheimer’s spots, macular petechiae, canbe identified on the soft palate. Often there iscoexistent tender lymphadenopathy, especially ofthe occipital, posterior auricular, and cervicalchains. Rubella is generally self-limiting, butsevere complications may occur. Children aremore susceptible to thrombocytopenia, vasculitis,orchitis, neuronitis, and progressive panencepha-litis [80]. Neonatal infections in the first trimestercan result in congenital defects, fetal death, spon-taneous abortion, or premature delivery.Prevention is via vaccination, and, as previouslystated, is contraindicated in immunocompromisedpatients. Treatment of infection is supportive [3].2.5.4 Parvovirus B19Parvovirus B19 is a small, single-stranded DNA-containing virus causing a wide range of diseasesvarying from asymptomatic infections to fetal
  16. 16. 34 E. Stamell and K. Krishnamurthydemise. The most common form of infection iserythema infectiosum, or “fifth disease.” In gen-eral, regardless of the clinical presentation, thevirus is self-limited with the exception of a fewcircumstances [80]. The peak incidence of infec-tion occurs in the winter and spring. It is trans-mitted through respiratory secretions, bloodproducts, or vertically during pregnancy.Although parvovirus B19 is more common inchildren, infection does occur in adults with vary-ing clinical presentation. The seroprevalance ofparvovirus B19 antibodies increases with age—up to 15% of children 1–5 years of age areaffected versus up to 80% of adults [5].Erythema infectiosum occurs after a 4–14-day incubation period. Individuals develop theclassic “slapped-cheek” facial erythema thatspares the nasal bridge and circumoral regions.One to four days later, erythematous maculesand papules appear which progress to form alacy, reticulate pattern most commonlyobserved on the extremities, lasting 1–3 weeks.Once cutaneous signs appear, the individual isno longer contagious [5, 80]. Arthralgia orarthritis, seen in up to 10% of patients witherythema infectiosum, is more common infemale adults and may occur in up to 60% ofthose infected [109].Both children and adults may develop a dis-tinct syndrome known as papular purpuric gloveand socks syndrome which is also secondary toparvovirus B19. Clinically, patients have edemaand erythema of the palms and soles with pete-chiae and purpura associated with burning andpruritus [5].Parvovirus B19 can cause complications inthree situations: immunosuppression, pregnancy,and underlying hematologic disease. Patients withhematologic disease, such as sickle cell anemia orhereditary spherocytosis, who become infectedwith parvovirus B19 are at risk of developingsevere transient aplastic anemia. In general, recov-ery is usually spontaneous, but heart failure anddeath may occur. Thrombocytopenia is anotherless common complication. Fetal infection withparvovirus B19 can result in miscarriage or non-immune hydrops fetalis [80]. The greatest risk tothe fetus is when infection is acquired before 20weeks gestation. Most fetal losses occur between20 and 28 weeks gestation [110].The mainstay of treatment is supportive.However, there are treatment modalities that havebeen used. High-dose IVIG have been shown toeliminate parvovirus B19 from the bone marrow.Intrauterine transfusions can reverse fetal anemiaand reduce fetal demise. Prevention and measuresto avoid susceptible people are often difficult asonce the rash appears and is recognized as parvovi-rus B19, patients are no longer contagious [3, 111].2.6 Fungal Infections2.6.1 Systemic CandidiasisCandida species are the most common cause offungal infections. While Candida albicans is themost common pathogen in oropharyngeal andcutaneous candidiasis, other species of Candidahave been isolated in a rising number of infec-tions in both invasive and vaginal candidiasis[112]. Systemic candidiasis is a fatal infectionthat is increasing in incidence, especially inimmunocompromised patients. Risk factorsinclude chemotherapy, hematological diseases,and prolonged use of broad-spectrum antibiotics[113, 114].Cutaneous lesions occur in a minority ofpatients, but when present can aid in early diag-nosis and rapid initiation of appropriate treat-ment, especially since there is no specificdiagnostic tool for systemic candidiasis [113].Clinically, cutaneous lesions in systemic candidi-asis begin as macules that develop into papules,pustules, or nodules with a surrounding ery-thematous halo. The lesions are common on thetrunk and extremities. Purpura can be seen inpatients with or without thrombocytopenia [113].Tissue culture may isolate the fungi.Antifungal medications should be started oncesystemic candidiasis is suspected. Fluconazole isthe treatment of choice for C. albicans; however,other species of Candida require amphotericin Bdeoxycholate [113, 115]. The mortality rate asso-ciated with systemic candidiasis ranges from 46to 75% [116].
  17. 17. 352 Infectious Emergencies in Dermatology2.6.2 MucormycosisMucormycosis, previously encompassed by thenow obsolete term zygomycosis, is a potentiallylife-threatening fungal infection [117].Mucormycosis is caused by fungi in the orderMucorales and the family Mucoraceae. The genuscontains over 3,000 species; however, not allcause disease in humans. The most commonlyisolated genera include Rhizopus, Mucor,Rhizomucor, and Absidia [118]. Disease can beclassified as rhino-orbital-cerebral, pulmonary,cutaneous, gastrointestinal, or disseminatedforms, and the host influences which form of dis-ease develops. Immunocompromised individualsare most susceptible to mucormycosis. Diabeticscommonly present with the rhino-orbital-cerebralform. Those individuals receiving deferoxamineare more susceptible to pulmonary, followed byrhinocerebral, and finally disseminated disease.Ferric complex of deferoxamine stimulates ironuptake and growth of Rhizopus. [119, 120].Cerebral disease is most commonly seen inintravenous drug users, and solid-organ trans-plant patients may develop pulmonary or rhino-orbital-cerebral disease [119, 121]. RecentlyApophysomyces elegans, a pathogen causingmucormycosis, has led to primary cutaneous andrhino-orbital-cerebral disease in immunocompe-tent patients [122]. This section covers the rhino-orbital-cerebral, cutaneous, and disseminatedforms of disease.Rhino-orbital-cerebral disease can present asrhinosinusitis, sinusitis, rhino-orbital, or rhinoc-erebral disease. Clinically, rapid development oftissue necrosis is seen in invasive mucormycosisdue to vascular invasion and thrombosis [117].Progressive disease is seen with necrosis or escharformation in the nasal cavity or on the palate.Patients can also develop trigeminal and facialcranial nerve palsy, ophthalmoplegia, epidural orsubdural abscesses, and cavernous or sagittalsinus thrombosis [117].Cutaneous mucormycosis develops after directspore inoculation in a wound. Initially, patientsdevelop erythema and induration of the skin,which progresses to necrosis with a black eschar[117]. Disseminated disease develops in patientswith cerebral, cutaneous, or pulmonary mucormy-cosis [119].Diagnosis of cutaneous lesions can be confirmedby histopathologic examination, revealing wide-angledbranchingfungalhyphae.Potassiumhydrox-ide preparations can be used to identify the hyphaefrom bronchoalveolar lavage samples. Blood cul-tures are often negative, even when the diagnosis isconfirmed with hyphae on histology [3].It is important to be aware of risk factors forthe development of mucormycosis as treatmentincludes reversal of these underlying risk factorsif present. Risk factors include long-termneutropenia, high-dose glucocorticoid therapy,hyperglycemia, diabetes with or withoutketoacidosis, iron overload, and use of defoxam-ine treatment [117]. Early diagnosis is requiredfor successful treatment of mucormycosis withprompt administration of antifungal therapy andsurgical debridement in select patients [123]. Onestudy found that a greater than 6-day delay intreatment with intravenous amphotericin-B0.5–1 mg/kg/day after diagnosis led to a doubledmortality rate at 12 weeks [124].2.6.3 HistoplasmosisHistoplasmosis, caused by the dimorphic fungusHistoplasma capsulatum var. capsulatum, is acommon infection in Southeastern and CentralUnited States. Birds and bats serve as reservoirsfor histoplasmosis, and their feces contain theorganism. Individuals acquire the disease eitherthrough inhalation or, less commonly, by directcutaneous inoculation of the fungus. Whileimmunocompromised individuals are at a higherrisk for disseminated histoplasmosis, immuno-competent hosts can become infected if the expo-sure is significant [3].Clinical presentations range from primary cuta-neous to pulmonary to disseminated histoplasmo-sis. The latter is covered in this section as it is theonly clinical presentation of histoplasmosis thatwould constitute a dermatologic emergency. Mostpatients infected with histoplasmosis experienceasymptomatichematogenousdisseminationthroughmacrophages infected with the parasite [125]. Risk
  18. 18. 36 E. Stamell and K. Krishnamurthyfactors for developing disseminated disease includeyoung age, AIDS, hematologic malignancies, solidorgan transplant, hematopoietic stem cell transplant,immunosuppressive agents, and congenital T-celldeficiencies [126]. Patients often have fever, mal-aise, anorexia, and weight loss. Cutaneous findingsin disseminated histoplasmosis are nonspecific.They vary from mucocutaneous oral ulcers or ero-sions to erythematous or molluscum-like papules ornodules [3, 127].The most common extracutaneoussites for disseminated involvement are the lung,spleen, lymph nodes, bone marrow, and liver; how-ever, any organ system can be involved. Severe dis-seminated disease can present as sepsis withhypotension, disseminated intravascular coagula-tion, renal failure, and acute respiratory distress[126]. Uncommonly, patients can develop endo-carditis, central nervous system infection, orAddison’s disease when there is destruction of bilat-eral adrenal glands by the fungus [126, 128].Laboratory abnormalities are nonspecific, butwill often include elevated alkaline phosphataselevels, pancytopenia, an increased sedimentationrate, elevated C-reactive protein levels, high lac-tate dehydrogenase levels, hypercalcemia, andincreased ferritin expression [125, 126]. Thefungi can be cultured in the blood, but the diag-nosis of disseminated histoplasmosis can beobtained by tissue biopsy of any involved site,revealing intracellular yeast forms surrounded bya rim of clearing [3, 129].Treatment is not indicated in self-limitedinfections. However, disseminated histoplasmo-sis requires systemic antifungal therapy (ampho-tericin B 0.7–1 mg/kg/day or itraconazole200–400 mg daily) [3].2.7 Parasitic Infections2.7.1 American Trypanosomiasis(Chagas Disease)Chagas disease, also known as American try-panosomiasis, is caused by the parasiteTrypanosoma cruzi, which is found in tropicalzones of theAmericas. The parasite is transmittedby the reduviid bug, which constitutes three mainspecies: Triatoma infestans, Rhodnius prolixus,and Panstronglus megistus [130]. Transmissionoccurs when a prior wound or an intact mucousmembrane is inoculated with the feces of aninfected bug [131].Chagas disease occurs in two main phases:the acute and chronic phases [132].Acute Chagasdisease develops after a 1–2-week incubationperiod and begins with a macular or papulonodu-lar, erythematous to violet, hard, painless lesionat the inoculation site [3]. Inoculation throughthe conjunctiva results in nonpainful, unilateraledema of the upper and lower eyelid for severalweeks, known as Romaña’s sign [131]. Thelesion may ulcerate, but usually regresses in 3weeks. A maculopapular, morbilliform, or urti-carial eruption may also be seen. Associatedsigns of acute infection include satellite lymph-adenitis, fever, myalgia, and hepatosplenomeg-aly [3]. The acute phase lasts for 4–8 weeks[131].Without successful treatment, the patient cango on to develop chronic Chagas disease [131].The chronic form is characterized by cardiac andgastrointestinal manifestations. Early cardiacfindings include conduction-system abnormalitiesand ventricular wall-motion abnormalities [130].After time, patients progress to high-degree heartblock, sustained and nonsustained ventriculartachycardia, sinus-node dysfunction, apical aneu-rysm, embolic phenomena, and progressivedilatedcardiomyopathy[133].Withthesefindings,there is a high risk of sudden death [134].Gastrointestinal Chagas disease involves theesophagus, colon, or both. Uncommon findingsare megaesophagus and megacolon [135].Diagnosis during the acute phase is made bydirect examination of Giemsa-stained bloodsmears, touch preps, or lymph-node biopsy. Inthe chronic phase, direct immunofluorescenceand PCR for anti-T. cruzi immunoglobulin Mantibodies can be diagnostic [132].Treatment with benznidazole 5 mg/kg/dayor nifurtimox 8–10 mg/kg/day in 3–4 doseshas been shown to reduce the severity of symp-tom and shorten the clinical course during theacute infection. The cure rate during the acutephase is between 60 and 85% [130]. Theefficacy of treatment for chronic infection isunclear [136].
  19. 19. 372 Infectious Emergencies in Dermatology2.7.2 Mucocutaneous LeishmaniasisLeishmaniasis, caused by protozoa in the genusLeishmania, encompasses three clinical forms:cutaneous, mucocutaneous, and visceral leishma-niasis. Although leishmaniasis is endemic inSouthern Europe, Central and South America,Africa, the Middle East, and South Asia, it isincreasingly seen in non-endemic regions in thesetting of travel to endemic countries [137].Leishmania, an intracellular parasite that targetsmacrophages, dendritic cells, and neutrophils, istransmitted via the bite of an infected female sandfly, primarily Phlebotomus (Old World) andLutzomyia (New World) [138, 139].While cutaneous leishmaniasis is generallybenign and self-limiting, mucocutaneous leish-maniasis is a potentially life-threatening infec-tionthatrequirestreatment[138].Theprogressionto mucosal disease depends on the virulence ofthe parasite as well as the individual cell-mediatedimmunity. Only 1–10% of infected patientswill develop mucosal involvement [140].Immunodeficiency is not necessarily a predispos-ing factor [141].Patients with mucocutaneous leishmaniasiswill often have a history of cutaneous leishmani-asis starting 1–5 years prior to the mucosalinvolvement. The primary cutaneous lesion isgenerally ulcerative and can be solitary or multi-ple [140]. Persistent nasal congestion is the mostcommon presenting symptom [141]. As the dis-ease progresses, patients develop erythema, ero-sions, and ulcers around the nares and lipsfollowed by lesions on the oropharynx, and occa-sionally widespread cutaneous disease [137](Fig. 2.8). Later in the disease course, patientscan have nasal septal perforation and palatalulceration with eventual destruction of the orona-sopharyngeal mucosa and cartilaginous facialand upper airway structures [137, 138]. Otherfindings include lymphadenopathy, fever, andhepatomegaly [137].Histopathology and touch preparations arediagnostic in cutaneous leishmaniasis; however,biopsy is necessary in mucocutaneous diseaseas there are very few parasites in the nasalmucosa. Diagnosis is confirmed by the presenceof intracellular amastigotes, but often specimenswill show granulomas [141]. When suspicion ishigh and biopsy only shows granulomas, PCRmay be used to isolate Leishmania DNA [142].Pentavalent antimony is first-line therapy fol-lowed by amphotericin B 0.5–1 mg/kg/day [143].All photographs used in this chapter are withpermission and courtesy of Michael Fisher, M.D.References1. Singh G, Sinha SK, Adhikary S, Babu KS, Ray P,Khanna SK. Necrotising infections of soft tissues—aclinical profile. Eur J Surg. 2002;168(6):366–71.2. Hasham S, Matteucci P, Stanley PR, Hart NB.Necrotising fasciitis. BMJ. 2005;330(7495):830–3.3. Wolf R, Davidovici BB, Parish JL, Parish LC.Emergency dermatology. New York: CambridgeUniversity Press; 2010.4. Elliott DC, Kufera JA, Myers RA. Necrotizing soft tis-sue infections. Risk factors for mortality and strategiesfor management. Ann Surg. 1996;224(5):672–83.5. Bolognia J, Jorizzo JL, Rapini RP. Dermatology. St.Louis, MO: Mosby Elsevier; 2008.6. Jallali N, Withey S, Butler PE. Hyperbaric oxygen asadjuvant therapy in the management of necrotizingfasciitis. Am J Surg. 2005;189(4):462–6.7. Kaul R, McGeer A, Norrby-Teglund A, Kotb M,Schwartz B, O’Rourke K, Talbot J, Low DE.Intravenous immunoglobulin therapy for streptococ-cal toxic shock syndrome—a comparative observa-tional study. The Canadian Streptococcal StudyGroup. Clin Infect Dis. 1999;28(4):800–7.8. Darenberg J, Ihendyane N, Sjolin J, Aufwerber E,Haidl S, Follin P, Andersson J, Norrby-Teglund A.Intravenous immunoglobulin G therapy in strepto-coccal toxic shock syndrome: a European random-ized, double-blind, placebo-controlled trial. ClinInfect Dis. 2003;37(3):333–40.Fig. 2.8 Mucocutaneous leishmaniasis
  20. 20. 38 E. Stamell and K. Krishnamurthy9. Huang KF, Hung MH, Lin YS, Lu CL, Liu C, ChenCC, Lee YH. Independent predictors of mortality fornecrotizing fasciitis: a retrospective analysis in asingle institution. J Trauma. 2011;71(2):467–73.10. Givner LB. Periorbital versus orbital cellulitis.Pediatr Infect Dis J. 2002;21(12):1157–8.11. Rudloe TF, Harper MB, Prabhu SP, Rahbar R,Vanderveen D, Kimia AA. Acute periorbital infec-tions: who needs emergent imaging? Pediatrics.2010;125(4):e719–26.12. Mahalingam-Dhingra A, Lander L, Preciado DA,Taylormoore J, Shah RK. Orbital and periorbitalinfections: a national perspective. Arch OtolaryngolHead Neck Surg. 2011;137(8):769–73.13. Hasanee K, Sharma S. Ophthaproblem. Orbital cel-lulitis. Can Fam Physician. 2004;50(359):365–7.14. Carfrae MJ, Kesser BW. Malignant otitis externa.Otolaryngol Clin North Am. 2008;41(3):537–49.viii–ix.15. Rosenstein NE, Perkins BA, Stephens DS, PopovicT, Hughes JM. Meningococcal disease. N Engl JMed. 2001;344(18):1378–88.16. Milonovich LM. Meningococcemia: epidemiology,pathophysiology, and management. J Pediatr HealthCare. 2007;21(2):75–80.17. Sexton K, Lennon D, Oster P, Aaberge I, Martin D,Reid S, Wong S, O’Hallahan J. Proceedings of theMeningococcal Vaccine Strategy World HealthOrganization satellite meeting, 10 March 2004,Auckland, New Zealand. N Z Med J.2004;117(1200):1. p preceding U1027.18. Ramos-e-Silva M, Pereira AL. Life-threateningeruptions due to infectious agents. Clin Dermatol.2005;23(2):148–56.19. James WD, Elston DM, Berger TG, Andrews GC.Andrews’ diseases of the skin: clinical dermatology.London: Saunders Elsevier; 2011.20. Healy CM, Baker CJ. The future of meningococcalvaccines. Pediatr Infect Dis J. 2005;24(2):175–6.21. Usatine RP, Sandy N. Dermatologic emergencies.Am Fam Physician. 2010;82(7):773–80.22. Dumler JS, Walker DH. Rocky Mountain spottedfever–changing ecology and persisting virulence.N Engl J Med. 2005;353(6):551–3.23. Dantas-Torres F. Rocky Mountain spotted fever.Lancet Infect Dis. 2007;7(11):724–32.24. Spach DH, Liles WC, Campbell GL, Quick RE,Anderson Jr DE, Fritsche TR. Tick-borne diseases inthe United States. N Engl J Med.1993;329(13):936–47.25. Helmick CG, Bernard KW, D’Angelo LJ. RockyMountain spotted fever: clinical, laboratory, and epi-demiological features of 262 cases. J Infect Dis.1984;150(4):480–8.26. Parola P, Paddock CD, Raoult D. Tick-borne rick-ettsioses around the world: emerging diseases chal-lenging old concepts. Clin Microbiol Rev.2005;18(4):719–56.27. Gammons M, Salam G. Tick removal. Am FamPhysician. 2002;66(4):643–5.28. Lacz NL, Schwartz RA, Kapila R. Rocky Mountainspotted fever. J Eur Acad Dermatol Venereol.2006;20(4):411–7.29. Stanek G, Wormser GP, Gray J, Strle F. Lyme bor-reliosis. Lancet. 2011;379(9814):461–73.30. des Vignes F, Piesman J, Heffernan R, Schulze TL,Stafford 3rd KC, Fish D. Effect of tick removal ontransmission of Borrelia burgdorferi and Ehrlichiaphagocytophila by Ixodes scapularis nymphs.J Infect Dis. 2001;183(5):773–8.31. Huppertz HI, Bohme M, Standaert SM, Karch H,Plotkin SA. Incidence of Lyme borreliosis in theWurzburg region of Germany. Eur J Clin MicrobiolInfect Dis. 1999;18(10):697–703.32. Stanek G, Fingerle V, Hunfeld KP, Jaulhac B, KaiserR, KrauseA, KristoferitschW, O’Connell S, OrnsteinK, Strle F, Gray J. Lyme borreliosis: clinical casedefinitions for diagnosis and management in Europe.Clin Microbiol Infect. 2011;17(1):69–79.33. Halperin JJ. Nervous system Lyme disease. InfectDis Clin North Am. 2008;22(2):261–74. vi.34. Bhate C, Schwartz RA. Lyme disease: Part II.Management and prevention. J Am Acad Dermatol.2011;64(4):639–53. quiz 654, 653.35. Brown SL, Hansen SL, Langone JJ. Role of serologyin the diagnosis of Lyme disease. JAMA.1999;282(1):62–6.36. Branda JA, Aguero-Rosenfeld ME, Ferraro MJ,Johnson BJ, Wormser GP, Steere AC. 2-tiered anti-body testing for early and late Lyme disease usingonly an immunoglobulin G blot with the addition ofa VlsE band as the second-tier test. Clin Infect Dis.2010;50(1):20–6.37. Wormser GP, Dattwyler RJ, Shapiro ED, HalperinJJ, Steere AC, Klempner MS, Krause PJ, Bakken JS,Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS,Nadelman RB. The clinical assessment, treatment,and prevention of lyme disease, human granulocyticanaplasmosis, and babesiosis: clinical practiceguidelines by the Infectious Diseases Society ofAmerica. Clin Infect Dis. 2006;43(9):1089–134.38. Katz TM, Miller JH, Hebert AA. Insect repellents:historical perspectives and new developments. J AmAcad Dermatol. 2008;58(5):865–71.39. Nadelman RB, Nowakowski J, Fish D, Falco RC,Freeman K, McKenna D, Welch P, Marcus R,Aguero-Rosenfeld ME, Dennis DT, Wormser GP.Prophylaxis with single-dose doxycycline for theprevention of Lyme disease after an Ixodes scapu-laris tick bite. N Engl J Med. 2001;345(2):79–84.40. Vazquez M, Muehlenbein C, Cartter M, Hayes EB,Ertel S, Shapiro ED. Effectiveness of personal pro-tective measures to prevent Lyme disease. EmergInfect Dis. 2008;14(2):210–6.41. Moayeri M, Leppla SH. The roles of anthrax toxin inpathogenesis. Curr Opin Microbiol. 2004;7(1):19–24.42. Wenner KA, Kenner JR. Anthrax. Dermatol Clin.2004;22(3):247–56. v.43. SwartzMN.Recognitionandmanagementofanthrax–an update. N Engl J Med. 2001;345(22): 1621–6.
  21. 21. 392 Infectious Emergencies in Dermatology44. Inglesby TV, O’Toole T, Henderson DA, Bartlett JG,Ascher MS, Eitzen E, Friedlander AM, GerberdingJ, Hauer J, Hughes J, McDade J, Osterholm MT,Parker G, Perl TM, Russell PK, Tonat K. Anthrax asa biological weapon, 2002: updated recommenda-tions for management. JAMA.2002;287(17):2236–52.45. Dixon TC, Meselson M, Guillemin J, Hanna PC.Anthrax. N Engl J Med. 1999;341(11):815–26.46. Inglesby TV, Henderson DA, Bartlett JG, AscherMS, Eitzen E, Friedlander AM, Hauer J, McDade J,Osterholm MT, O’Toole T, Parker G, Perl TM,Russell PK, Tonat K. Anthrax as a biologicalweapon: medical and public health management.Working Group on Civilian Biodefense. JAMA.1999;281(18):1735–45.47. Evans ME, Gregory DW, Schaffner W, McGee ZA.Tularemia: a 30-year experience with 88 cases.Medicine (Baltimore). 1985;64(4):251–69.48. McGinley-Smith DE, Tsao SS. Dermatoses fromticks. J Am Acad Dermatol. 2003;49(3):363–92.quiz 393–6.49. Choi E. Tularemia and Q fever. Med Clin North Am.2002;86(2):393–416.50. Dana AN. Diagnosis and treatment of tick infesta-tion and tick-borne diseases with cutaneous manifes-tations. Dermatol Ther. 2009;22(4):293–326.51. Amagai M, Matsuyoshi N, Wang ZH, Andl C,Stanley JR. Toxin in bullous impetigo and staphylo-coccal scalded-skin syndrome targets desmoglein 1.Nat Med. 2000;6(11):1275–7.52. Odom RB, James WD, Berger TG. Andrews’ dis-eases of the skin: clinical dermatology. St. Louis,MO: Mosby; 2000.53. Cribier B, Piemont Y, Grosshans E. Staphylococcalscalded skin syndrome in adults. A clinical reviewillustrated with a new case. J Am Acad Dermatol.1994;30(2 Pt 2):319–24.54. Murray RJ. Recognition and management ofStaphylococcus aureus toxin-mediated disease.Intern Med J. 2005;35 Suppl 2:S106–19.55. Gemmell CG. Staphylococcal scalded skin syn-drome. J Med Microbiol. 1995;43(5):318–27.56. Macias ES, Pereira FA, Rietkerk W, Safai B.Superantigens in dermatology. J Am Acad Dermatol.2011;64(3):455–72. quiz 473–4.57. Lappin E, Ferguson AJ. Gram-positive toxic shocksyndromes. Lancet Infect Dis. 2009;9(5):281–90.58. Schlievert PM, Blomster DA. Production of staphy-lococcal pyrogenic exotoxin type C: influence ofphysical and chemical factors. J Infect Dis.1983;147(2):236–42.59. Bohach GA, Fast DJ, Nelson RD, Schlievert PM.Staphylococcal and streptococcal pyrogenic toxinsinvolved in toxic shock syndrome and related ill-nesses. Crit Rev Microbiol. 1990;17(4):251–72.60. Fraser JD, Proft T. The bacterial superantigen andsuperantigen-like proteins. Immunol Rev.2008;225:226–43.61. Stevens DL. Streptococcal toxic shock syndrome.Clin Microbiol Infect. 2002;8(3):133–6.62. McCormick JK, Yarwood JM, Schlievert PM. Toxicshock syndrome and bacterial superantigens: anupdate. Annu Rev Microbiol. 2001;55:77–104.63. Kato K, Sakamoto T, Ito K. Gamma-globulin inhib-its superantigen-induced lymphocyte proliferationand cytokine production. Allergol Int. 2007;56(4):439–44.64. Adcock DM, Brozna J, Marlar RA. Proposedclassification and pathologic mechanisms of purpurafulminans and skin necrosis. Semin Thromb Hemost.1990;16(4):333–40.65. Carpenter CT, Kaiser AB. Purpura fulminans inpneumococcal sepsis: case report and review. ScandJ Infect Dis. 1997;29(5):479–83.66. Adcock DM, Hicks MJ. Dermatopathology of skinnecrosis associated with purpura fulminans. SeminThromb Hemost. 1990;16(4):283–92.67. Betrosian AP, Berlet T, Agarwal B. Purpura fulmin-ans in sepsis. Am J Med Sci. 2006;332(6):339–45.68. Varon J, Chen K, Sternbach GL. Rupert Waterhouseand Carl Friderichsen: adrenal apoplexy. J EmergMed. 1998;16(4):643–7.69. Zomorrodi A, Wald ER. Ecthyma gangrenosum:considerations in a previously healthy child. PediatrInfect Dis J. 2002;21(12):1161–4.70. Baro M, Marin MA, Ruiz-Contreras J, de Miguel SF,Sanchez-Diaz I. Pseudomonas aeruginosa sepsis andecthymagangrenosumasinitialmanifestationsofprimaryimmunodeficiency. Eur J Pediatr. 2004;163(3):173–4.71. Wong SN, Tam AY, Yung RW, Kwan EY, Tsoi NN.Pseudomonas septicaemia in apparently healthychildren. Acta Paediatr Scand. 1991;80(5):515–20.72. Bettens S, Delaere B, Glupczynski Y, SchoevaerdtsD, Swine C. Ecthyma gangrenosum in a non-neutro-paenic, elderly patient: case report and review of theliterature. Acta Clin Belg. 2008;63(6):394–7.73. Gucluer H, Ergun T, Demircay Z. Ecthyma gan-grenosum. Int J Dermatol. 1999;38(4):299–302.74. Brown ZA, Wald A, Morrow RA, Selke S, Zeh J,Corey L. Effect of serologic status and cesarean deliv-ery on transmission rates of herpes simplex virus frommother to infant. JAMA. 2003;289(2): 203–9.75. Kimberlin DW. Neonatal herpes simplex infection.Clin Microbiol Rev. 2004;17(1):1–13.76. Yeager AS, Arvin AM. Reasons for the absence of ahistory of recurrent genital infections in mothers ofneonates infected with herpes simplex virus.Pediatrics. 1984;73(2):188–93.77. Brown ZA, Selke S, Zeh J, Kopelman J, Maslow A,Ashley RL, Watts DH, Berry S, Herd M, Corey L.The acquisition of herpes simplex virus during preg-nancy. N Engl J Med. 1997;337(8):509–15.78. Whitley RJ, Corey L,ArvinA, Lakeman FD, SumayaCV, Wright PF, Dunkle LM, Steele RW, Soong SJ,Nahmias AJ, et al. Changing presentation of herpessimplex virus infection in neonates. J Infect Dis.1988;158(1):109–16.
  22. 22. 40 E. Stamell and K. Krishnamurthy79. Arvin AM, Yeager AS, Bruhn FW, Grossman M.Neonatal herpes simplex infection in the absence ofmucocutaneous lesions. J Pediatr. 1982;100(5):715–21.80. Rebora A. Life-threatening cutaneous viral diseases.Clin Dermatol. 2005;23(2):157–63.81. Kusuhara T, Nakajima M, Inoue H, Takahashi M,Yamada T. Parainfectious encephalomyeloradiculitisassociated with herpes simplex virus 1 DNA in cere-brospinal fluid. Clin Infect Dis. 2002;34(9):1199–205.82. Fatahzadeh M, Schwartz RA. Human herpes sim-plex virus infections: epidemiology, pathogenesis,symptomatology, diagnosis, and management. J AmAcad Dermatol. 2007;57(5):737–63. quiz 764–6.83. Marcus B, Lipozencic J, Matz H, Orion E, Wolf R.Herpes simplex: autoinoculation versus dissemination.Acta Dermatovenerol Croat. 2005;13(4): 237–41.84. Sanderson IR, Brueton LA, Savage MO, Harper JI.Eczema herpeticum: a potentially fatal disease. BrMed J (Clin Res Ed). 1987;294(6573):693–4.85. Enders G, Miller E, Cradock-Watson J, Bolley I,Ridehalgh M. Consequences of varicella and herpeszoster in pregnancy: prospective study of 1739 cases.Lancet. 1994;343(8912):1548–51.86. Smith CK, Arvin AM. Varicella in the fetus and new-born. Semin Fetal Neonatal Med. 2009;14(4):209–17.87. Chapman SJ. Varicella in pregnancy. SeminPerinatol. 1998;22(4):339–46.88. Selleger C. [Fatal varicella pneumonia in adults.Report of two cases and review of literature (author’stransl)]. Rev Fr Mal Respir. 1979;7(1):9–18.89. Grose C. Varicella vaccination of children in theUnited States: assessment after the first decade1995–2005. J Clin Virol. 2005;33(2):89–95. discus-sion 96–8.90. Marin M, Meissner HC, Seward JF. Varicella pre-vention in the United States: a review of successesand challenges. Pediatrics. 2008;122(3):e744–51.91. Gnann Jr JW. Varicella-zoster virus: atypical presen-tations and unusual complications. J Infect Dis.2002;186 Suppl 1:S91–8.92. GildenDH,Kleinschmidt-DeMastersBK,LaGuardiaJJ, Mahalingam R, Cohrs RJ. Neurologic complica-tions of the reactivation of varicella-zoster virus. NEngl J Med. 2000;342(9):635–45.93. Sweeney CJ, Gilden DH. Ramsay Hunt syndrome. JNeurol Neurosurg Psychiatry. 2001;71(2):149–54.94. Murakami S, Hato N, Horiuchi J, Honda N, Gyo K,Yanagihara N. Treatment of Ramsay Hunt syndromewith acyclovir-prednisone: significance of earlydiagnosis and treatment. Ann Neurol. 1997;41(3):353–7.95. Uscategui T, Doree C, Chamberlain IJ, Burton MJ.Corticosteroids as adjuvant to antiviral treatment inRamsay Hunt syndrome (herpes zoster oticus withfacial palsy) in adults. Cochrane Database SystRev.2008;CD006852.96. Sanjay S, Huang P, Lavanya R. Herpes zoster oph-thalmicus. Curr Treat Options Neurol.2011;13(1):79–91.97. Liesegang TJ. Herpes zoster ophthalmicus naturalhistory, risk factors, clinical presentation, and mor-bidity. Ophthalmology. 2008;115(2 Suppl):S3–12.98. Zaal MJ, Volker-Dieben HJ, D’Amaro J. Prognosticvalue of Hutchinson’s sign in acute herpes zosterophthalmicus. Graefes Arch Clin Exp Ophthalmol.2003;241(3):187–91.99. Harding SP. Management of ophthalmic zoster.J Med Virol. 1993;(Suppl 1):97–101.100. Dworkin RH, Johnson RW, Breuer J, Gnann JW,Levin MJ, Backonja M, Betts RF, Gershon AA,Haanpaa ML, McKendrick MW, Nurmikko TJ,Oaklander AL, Oxman MN, Pavan-Langston D,Petersen KL, Rowbotham MC, Schmader KE, StaceyBR, Tyring SK, van WijckAJ, Wallace MS, WassilewSW, Whitley RJ. Recommendations for the manage-ment of herpes zoster. Clin Infect Dis. 2007;44 Suppl1:S1–26.101. Arnou R, Fiquet A, Thomas S, Sadorge C.Immunogenicity and safety of ZOSTAVAX(R)approaching expiry potency in individuals aged>/=50 years. Hum Vaccin. 2011;7(10):1060–5.102. Sanford M, Keating GM. Zoster vaccine (Zostavax):a review of its use in preventing herpes zoster andpostherpetic neuralgia in older adults. Drugs Aging.2010;27(2):159–76.103. Thomas B, Farquhar-Smith P. Extended-releasegabapentin in post-herpetic neuralgia. Expert OpinPharmacother. 2011;12(16):2565–71.104. Adler SP, Marshall B. Cytomegalovirus infections.Pediatr Rev. 2007;28(3):92–100.105. Cutts FT, Henao-Restrepo A, Olive JM. Measleselimination: progress and challenges. Vaccine.1999;17 Suppl 3:S47–52.106. Epidemiology of measles—United States, 2001–2003. MMWR Morb Mortal Wkly Rep.2004;53(31):713–716.107. Scott LA, Stone MS. Viral exanthems. DermatolOnline J. 2003;9(3):4.108. Hussey GD, Klein M. A randomized, controlled trialof vitamin A in children with severe measles. N EnglJ Med. 1990;323(3):160–4.109. Balkhy HH, Sabella C, Goldfarb J. Parvovirus: areview. Bull Rheum Dis. 1998;47(3):4–9.110. Norbeck O, Papadogiannakis N, Petersson K, HirbodT, Broliden K, Tolfvenstam T. Revised clinical pre-sentation of parvovirus B19-associated intrauterinefetal death. Clin Infect Dis. 2002;35(9):1032–8.111. Katta R. Parvovirus B19: a review. Dermatol Clin.2002;20(2):333–42.112. Rex JH, Walsh TJ, Sobel JD, Filler SG, Pappas PG,Dismukes WE, Edwards JE. Practice guidelines forthe treatment of candidiasis. Infectious DiseasesSociety of America. Clin Infect Dis. 2000;30(4):662–78.113. Pedraz J, Delgado-Jimenez Y, Perez-Gala S, Nam-Cha S, Fernandez-Herrera J, Garcia-Diez A.Cutaneous expression of systemic candidiasis. ClinExp Dermatol. 2009;34(1):106–10.114. Pagano L, Mele L, Fianchi L, Melillo L, Martino B,D’Antonio D, Tosti ME, Posteraro B, Sanguinetti M,
  23. 23. 412 Infectious Emergencies in DermatologyTrape G, Equitani F, Carotenuto M, Leone G.Chronic disseminated candidiasis in patients withhematologic malignancies. Clinical features and out-come of 29 episodes. Haematologica. 2002;87(5):535–41.115. Ratip S, Odabasi Z, Karti S, Cetiner M, Yegen C,Cerikcioglu N, Bayik M, Korten V. Clinical micro-biological case: chronic disseminated candidiasisunresponsive to treatment. Clin Microbiol Infect.2002;8(7):435–6. 442–34.116. Uzun O, Ascioglu S, Anaissie EJ, Rex JH. Risk fac-tors and predictors of outcome in patients with can-cer and breakthrough candidemia. Clin Infect Dis.2001;32(12):1713–7.117. Sun HY, Singh N. Mucormycosis: its contemporaryface and management strategies. Lancet Infect Dis.2011;11(4):301–11.118. Reyes HM, Tingle EJ, Fenves AZ, Spiegel J, BurtonEC. Pulmonary invasive mucormycosis in a patientwith secondary iron overload following deferoxam-ine therapy. Proc (Bayl Univ Med Cent).2008;21(4):378–81.119. Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA,Sarkisova TA, Schaufele RL, Sein M, Sein T, ChiouCC,ChuJH,KontoyiannisDP,WalshTJ.Epidemiologyand outcome of zygomycosis: a review of 929 reportedcases. Clin Infect Dis. 2005;41(5):634–53.120. Van Cutsem J, Boelaert JR. Effects of deferoxamine,feroxamine and iron on experimental mucormycosis(zygomycosis). Kidney Int. 1989;36(6):1061–8.121. Almyroudis NG, Sutton DA, Linden P, Rinaldi MG,Fung J, Kusne S. Zygomycosis in solid organ trans-plant recipients in a tertiary transplant center andreview of the literature. Am J Transplant.2006;6(10):2365–74.122. Liang KP, Tleyjeh IM, Wilson WR, Roberts GD,Temesgen Z. Rhino-orbitocerebral mucormycosiscaused byApophysomyces elegans. J Clin Microbiol.2006;44(3):892–8.123. Spellberg B, Walsh TJ, Kontoyiannis DP, Edwards JrJ, Ibrahim AS. Recent advances in the managementof mucormycosis: from bench to bedside. Clin InfectDis. 2009;48(12):1743–51.124. Chamilos G, Lewis RE, Kontoyiannis DP. Delayingamphotericin B-based frontline therapy significantlyincreases mortality among patients with hematologicmalignancy who have zygomycosis. Clin Infect Dis.2008;47(4):503–9.125. Goodwin Jr RA, Shapiro JL, Thurman GH, ThurmanSS, Des Prez RM. Disseminated histoplasmosis:clinical and pathologic correlations. Medicine(Baltimore). 1980;59(1):1–33.126. Kauffman CA. Histoplasmosis: a clinical and labora-tory update. Clin Microbiol Rev. 2007;20(1): 115–32.127. Reddy P, Gorelick DF, Brasher CA, Larsh H.Progressive disseminated histoplasmosis as seen inadults. Am J Med. 1970;48(5):629–36.128. Smith JW, Utz JP. Progressive disseminated histo-plasmosis. A prospective study of 26 patients. AnnIntern Med. 1972;76(4):557–65.129. Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW,McKinsey DS, Loyd JE, Kauffman CA. Clinicalpractice guidelines for the management of patientswith histoplasmosis: 2007 update by the InfectiousDiseases Society of America. Clin Infect Dis.2007;45(7):807–25.130. Rassi Jr A, Rassi A, Marin-Neto JA. Chagas disease.Lancet. 2010;375(9723):1388–402.131. Bern C. Antitrypanosomal therapy for chronicChagas’ disease. N Engl J Med. 2011;364(26):2527–34.132. Lescure FX, Le Loup G, Freilij H, Develoux M,Paris L, Brutus L, Pialoux G. Chagas disease:changes in knowledge and management. LancetInfect Dis. 2010;10(8):556–70.133. Rassi Jr A, Rassi A, Little WC. Chagas’ heart dis-ease. Clin Cardiol. 2000;23(12):883–9.134. Rassi Jr A, Rassi SG, Rassi A. Sudden death inChagas’ disease. Arq Bras Cardiol. 2001;76(1):75–96.135. de Oliveira RB, Troncon LE, Dantas RO,Menghelli UG. Gastrointestinal manifestations ofChagas’ disease. Am J Gastroenterol. 1998;93(6):884–9.136. Marin-Neto JA, Rassi Jr A, Avezum Jr A, MattosAC, Rassi A, Morillo CA, Sosa-Estani S, Yusuf S.The BENEFIT trial: testing the hypothesis that try-panocidal therapy is beneficial for patients withchronic Chagas heart disease. Mem Inst OswaldoCruz. 2009;104 Suppl 1:319–24.137. David CV, Craft N. Cutaneous and mucocutaneousleishmaniasis. Dermatol Ther. 2009;22(6):491–502.138. Murray HW, Berman JD, Davies CR, Saravia NG.Advances in leishmaniasis. Lancet. 2005;366(9496):1561–77.139. Solbach W, Laskay T. The host response toLeishmania infection. Adv Immunol. 2000;74:275–317.140. Weigle K, Saravia NG. Natural history, clinical evo-lution, and the host-parasite interaction in NewWorld cutaneous Leishmaniasis. Clin Dermatol.1996;14(5):433–50.141. Ahluwalia S, Lawn SD, Kanagalingam J, GrantH, Lockwood DN. Mucocutaneous leishmaniasis:an imported infection among travellers to centraland South America. BMJ. 2004;329(7470):842–4.142. Scope A, Trau H, Bakon M, Yarom N, Nasereddin A,Schwartz E. Imported mucosal leishmaniasis in atraveler. Clin Infect Dis. 2003;37(6):e83–7.143. Amato VS, Tuon FF, Siqueira AM, Nicodemo AC,Neto VA. Treatment of mucosal leishmaniasis inLatin America: systematic review. Am J Trop MedHyg. 2007;77(2):266–74.
  24. 24. http://www.springer.com/978-1-4614-5030-6

×