Fever and Rash in the Immunocompetent Patient

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Fever and rash in the immunocompetent patient

Official reprint from UpToDate® www.uptodate.com ©2014 UpToDate® Fever and rash in the immunocompetent patient Authors Fred A Lopez, MD Charles V Sanders, MD

Section Editor Peter F Weller, MD, FACP

Deputy Editor Anna R Thorner, MD

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: May 2014. | This topic last updated: Jan 23, 2014. INTRODUCTION — Fever with an accompanying rash is a common symptom constellation in patients presenting to clinicians' offices and emergency departments. Skin manifestations may provide the only early clue to an underlying infection, may be the hallmark of contagious disease, and/or may be an early sign of a life-threatening infection. The differential diagnosis of fever and rash is extremely broad, but this symptom complex provides an opportunity for the diligent clinician to establish a probable etiology through a careful history and physical examination. A systematic approach is crucial for establishing a timely diagnosis, determining early therapy when appropriate, and considering isolation of the patient if necessary. Epidemiologic clues are important to pursue such as [1-6]: ● Age of the patient ● Season of the year ● Travel history ● Geographic location ● Exposures including to insects, animals, and ill contacts ● Medications ● Immunizations and history of childhood illnesses ● The immune status of the host Features of the rash are also important to consider, including: ● Characteristics of the lesions ● Distribution and progression of the rash ● Timing of the onset in relation to fever ● Change in morphology, such as papules to vesicles or petechiae Despite the strong association between the syndrome of fever and rash and infectious diseases, a variety of noninfectious processes can also cause similar presentations, including deep venous thrombosis, superficial thrombophlebitis, erythromelalgia, relapsing polychondritis, foreign body reactions, drug reactions, gouty arthritis, cutaneous lupus erythematosus, and erythema nodosum [7]. The approach to the immunocompetent patient with fever and rash and selected presentations that constitute emergencies will be reviewed here. Specific infections with characteristic rashes and fever and rash in immunocompromised patients are discussed separately. (See "Infectious causes of fever and rash in non-HIV immunocompromised hosts" and "Fever and rash in HIV-infected patients".) EPIDEMIOLOGY AND ETIOLOGY — Epidemiologic features are extremely helpful in the approach to a patient with a fever and rash [1-4]. Diseases that present in childhood — The age of the patient often assists in narrowing the differential diagnosis. Exanthems associated with a variety of viral illnesses are classically seen in the pediatric age group [8]. The constellation of symptoms and a characteristic rash often allow for a clinically based diagnosis, as illustrated by the following disorders. ● Measles (rubeola) is associated with a blanching erythematous "brick-red" maculopapular rash beginning in the head and neck area and spreading centrifugally to the trunk and extremities; patients also complain of fever, cough, coryza, and conjunctivitis (picture 1). (See "Clinical presentation and diagnosis of measles".) ● Chickenpox is characterized by classic vesicular lesions on an erythematous base that appear in crops and are present in different stages from papules through vesicles to crusting (picture 2). (See "Clinical features of varicella-zoster virus infection: Chickenpox".) ● Rubella has a rash that resembles measles, but the patient does not appear to be sick; prominent postauricular, posterior cervical, and/or suboccipital adenopathy also assists in the diagnosis. Forscheimer spots, or punctate soft palate macules, can represent a helpful clue. ● Erythema infectiosum (fifth disease) is due to human parvovirus B19. Children, unlike adults, often develop a characteristic rash with a "slapped cheeks" appearance (picture 3). (See "Clinical manifestations and pathogenesis of human parvovirus B19 infection".) ● Roseola infantum or exanthem subitum, a human herpesvirus 6 or 7 infection primarily seen in infants, is characterized by high fever for three to four days, followed by seizures and a generalized maculopapular rash that spreads from the trunk to the extremities but spares the face. (See "Roseola infantum (exanthem subitum)" and "Human herpesvirus 7 infection", section on 'Primary infection'.) Other infections accompanied by rash also occur primarily in children: ● Scarlet fever is an exotoxin (erythrogenic toxin)-mediated diffuse erythematous rash occurring most commonly in the setting of pharyngitis from group A Streptococcus (GAS) infection. Scarlet fever is manifested by a coarse, sandpaper-like, erythematous, http://www.uptodate.com/contents/fever-and-rash-in-the-immunocompetent-patient?topicKey=ID%2F2744&elapsedTimeMs=9&source=search_result&sear… 1/62

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Fever and rash in the immunocompetent patient

blanching rash, which ultimately desquamates. This is accompanied by circumoral pallor and a strawberry tongue. (See "Complications of streptococcal tonsillopharyngitis".) ● Acute rheumatic fever (ARF) is another potential sequela of group A streptococcal pharyngeal infection. The classic dermatologic manifestations of ARF are erythema marginatum (transient macular lesions with central clearing found on the extensor surfaces of the proximal extremities and trunk) and subcutaneous nodules often located over bony prominences. (See "Complications of streptococcal tonsillopharyngitis" and "Clinical manifestations and diagnosis of acute rheumatic fever".) ● Kawasaki syndrome, a disease of unknown etiology, is usually seen in children less than four years of age. In addition to fever lasting >5 days, some of the criteria for this syndrome, as defined by the Centers for Disease Control and Prevention (CDC), are bilateral conjunctival injection, injected or fissured lips, injected pharynx or 'strawberry tongue' (picture 4), erythema of the palms or soles, edema of the hands or feet, or generalized or periungual desquamation, rash, and cervical lymphadenopathy [9]. (See "Kawasaki disease: Clinical features and diagnosis".) ● Nonpolio enteroviruses (coxsackievirus, echovirus) can cause a variety of rashes and should always be included in the differential diagnosis of a young child with fever and rash of undetermined etiology. (See "Clinical manifestations and diagnosis of enterovirus and parechovirus infections".) ● An evaluation for Epstein-Barr virus (EBV)–associated infectious mononucleosis should be undertaken in older children and adolescents who present with fever, malaise, sweats, anorexia, nausea, chills, sore throat, posterior cervical lymphadenopathy, splenomegaly, and a maculopapular rash, especially after the administration of ampicillin (picture 5). The rash is usually over the trunk but can involve the extremities, including the hands and feet. Other causes of infectious mononucleosis are discussed below. (See 'Selected diseases that present in adulthood' below and "Infectious mononucleosis in adults and adolescents".) ● Adolescents and young adults with pharyngitis, fever, lymphadenopathy, and/or maculopapular/scarlatiniform rash whose work-up is negative for group A Streptococcus and viral-associated mononucleosis may be infected with Arcanobacterium haemolyticum, a grampositive rod that appears to be more susceptible to erythromycin than to penicillin [10]. This infection is seen primarily in patients who are 15 to 18 years of age, and the rash, which can be pruritic, is typically seen first over the extensor surfaces before spreading centrally [10]. The rash usually spares the face. ● Mycoplasma infection may be accompanied by skin findings, which include a mild erythematous maculopapular or vesicular rash, erythema multiforme, or the Stevens-Johnson syndrome. (See "Mycoplasma pneumoniae infection in children", section on 'Skin disease'.) Selected diseases that present in adulthood — Exanthems associated with a variety of viral illnesses can be seen in adults. Several to consider include: ● Measles (rubeola) is associated with a blanching erythematous "brick-red" maculopapular rash beginning in the head and neck area and spreading centrifugally to the trunk and extremities (picture 1); patients also complain of fever, cough, coryza, and conjunctivitis. Despite the availability of an effective measles vaccine, measles outbreaks continue to occur [11]. (See "Clinical presentation and diagnosis of measles" and "Epidemiology and transmission of measles".) ● Infectious mononucleosis can be caused by several different pathogens. Young adults who present with fever, malaise, sweats, anorexia, nausea, chills, sore throat, posterior cervical lymphadenopathy, splenomegaly, and a maculopapular rash, especially after the administration of ampicillin, should undergo an evaluation for Epstein-Barr virus (EBV)–associated infectious mononucleosis (picture 5). The rash is usually over the trunk but can involve the extremities, including the hands and feet. About half of all college freshmen have EBV-associated antibodies, and up to 20 percent of those who do not are expected to seroconvert annually during these years. Importantly, these cases are usually asymptomatic [12]. (See "Infectious mononucleosis in adults and adolescents".) Cytomegalovirus should be considered in the heterophile antibody-negative patient with infectious mononucleosis, although lymphadenopathy and pharyngitis may not be as prominent. The acute retroviral syndrome that may occur approximately two to four weeks after primary HIV infection is a mononucleosis-like illness characterized by fever, sore throat, malaise, headache, lymphadenopathy, mucocutaneous ulceration, and rash. The rash, seen in more than 50 percent of patients, is usually transient, maculopapular, nonpruritic, and truncal or facial in location. (See "Acute and early HIV infection: Pathogenesis and epidemiology".) Adolescents and young adults with pharyngitis, fever, lymphadenopathy, and/or a maculopapular/scarlatiniform rash whose evaluation is negative for group A Streptococcus and viral causes of mononucleosis may be infected with Arcanobacterium haemolyticum, a grampositive rod that appears to be more susceptible to erythromycin than to penicillin [10]. This infection is seen primarily in patients who are 15 to 18 years of age and the rash, which can be pruritic, is typically seen first over the extensor surfaces before spreading centrally [10]. The rash usually spares the face. ● Approximately 20 percent of cases of erythema infectiosum occur in adults [13]. Constitutional symptoms in primary infection are more pronounced in adults and typically include lymphadenopathy, arthritis, and fever. The rash, when present, is often described as first macular and then lacy and reticulated, spreading initially from the limbs to the trunk and buttocks. (See "Clinical manifestations and pathogenesis of human parvovirus B19 infection".) ● Individuals who did not have chickenpox during childhood may develop it later in life. Those who did have chickenpox may develop herpes zoster (shingles), which is caused by reactivation of latent varicella zoster virus. Incidence and severity increases with age and with increasing immunosuppression. In immunocompetent individuals, herpes zoster is typically manifested as vesicular lesions distributed along a dermatome and ending at the midline (picture 6). (See "Clinical features of varicella-zoster virus infection: Chickenpox" and "Clinical manifestations of varicella-zoster virus infection: Herpes zoster".) http://www.uptodate.com/contents/fever-and-rash-in-the-immunocompetent-patient?topicKey=ID%2F2744&elapsedTimeMs=9&source=search_result&sear… 2/62

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● Mycoplasma infection may be accompanied by skin findings, which range from a mild erythematous maculopapular or vesicular rash to the Stevens-Johnson syndrome. (See "Mycoplasma pneumoniae infection in adults", section on 'Skin disease'.) Season of the year — A number of infections characterized by fever and rash have a distinct seasonal predisposition. As examples, nonpolio enteroviral infections occur in the summer and fall months; Kawasaki syndrome, meningococcal infection, and parvoviral infections present most commonly in the winter or early spring months; measles and rubella are more frequent in the spring; tick-borne diseases such as Lyme disease, ehrlichiosis, and Rocky Mountain spotted fever (RMSF) primarily occur in the spring and summer; tularemia and plague are usually seen in the summer. Vibrio vulnificus infections occur between the months of April and October, when warmer waters facilitate propagation of this organism. Septicemia due to this organism typically occurs after consumption of raw seafood (usually oysters). Vibrio vulnificus– and V. parahaemolyticus–associated wound infections can occur after injury to skin in contaminated water (eg, after natural disasters) [14,15]. (See "Vibrio vulnificus infections".) Geography — Travel to or residence in specific areas of the continental United States or other parts of the world can provide important clues for the diagnosis of fever and rash [16-18]. Examples associated with a principal location in the United States include: ● Rocky Mountain spotted fever — South-central and Atlantic states ● Human monocytic ehrlichiosis — Midwestern, south-central, and southeastern states ● Lyme disease — The Pacific northwest, the midwest, and the northeast ● The tick vectors for tularemia — Western, southeastern, and south-central states ● Plague — Western states ● Relapsing fever due to Borrelia hermsii — Mountainous areas of the western United States ● Endemic fungal infections including Blastomyces dermatitidis (southeastern states), Coccidioides immitis (southwestern states), and Histoplasma capsulatum (Mississippi and Ohio River valleys) Several informative reviews on skin manifestations of infections in areas of the world other than the United States are available [19,20]. The CDC website (www.cdc.gov/travel/index.htm) is an excellent resource for prospective travelers to other areas of the world. (See "Travel advice".) A number of entities, characterized by rash but not always fever, merit consideration in individuals residing in or returning from trips to international sites [21,22]. ● Cutaneous leishmaniasis, which can present with papular, nodular, or ulcerative lesions, occurs in an Old World and New World form caused by different species. Leishmania tropica, L. major, or L. aethiopica occurs in patients who live in or who have visited the Middle East, Far East, or Africa (Old World cutaneous leishmaniasis) (picture 7). New World cutaneous leishmaniasis is caused by different species in Central and South America. L. braziliensis in South America causes ulcerative lesions with the subsequent development of disfiguring oral, pharyngeal, or nasal lesions. Leishmaniasis has also been reported in central and southern Texas in patients who have not traveled to areas endemic for this organism [23]. ● Trypanosoma cruzi, which causes Chagas disease, is found in South and Central America. Findings can include Romaña's sign, a combination of unilateral conjunctivitis and eyelid edema (picture 8) or the chagoma, an indurated nodular lesion. ● Skin manifestations of schistosomiasis, acquired by wading or swimming in fresh water, can include nonspecific maculopapular lesions or characteristic verrucoid lesions known as Bilharzia cutaneous tarda. The most common species infecting humans include Schistosoma haematobium (Africa, Middle East), S. mansoni (Africa, Middle East, South America), and S. japonicum (eastern Asia). In addition, in North America similar maculopapular lesions ("swimmer's itch") may develop after swimming or wading in water that contains cercariae of avian and other non-human schistosome species. (See "Epidemiology, pathogenesis, and clinical features of schistosomiasis", section on 'Swimmer's itch'.) ● Dengue virus infections are increasing in incidence, and its primary vector, the Aedes aegypti mosquito, inhabits nearly all tropical latitudes, including the United States [24]. Skin manifestations can include a transient macular rash early in the infection and a generalized morbilliform-like rash sparing the palms and soles when fever resolves on approximately day five. Petechiae, purpura, and ecchymoses are more likely to be seen in dengue hemorrhagic fever or dengue shock syndrome, severe presentations of dengue virus seen in previously sensitized patients [25]. (See "Clinical manifestations and diagnosis of dengue virus infections".) ● Chikungunya fever caused by the mosquito-transmitted chikungunya virus is characterized by fever, rash, painful polyarthralgias, headache, fatigue, myalgias, and gastrointestinal symptoms. The rash is typically described as macular, maculopapular, vesicular, bullous, or petechial [26,27]. Outbreaks have been reported in sub-Saharan Africa, southeast Asia and India, islands in the Indian Ocean, Italy, and the Caribbean. The average incubation period is three to seven days. (See "Chikungunya fever".) ● A variety of parasitic larvae can cause a "creeping eruption" known as cutaneous larva migrans. (See "Cutaneous larva migrans (creeping eruption)".) Typically, dog and cat hookworm larvae enter the skin of the foot and cause a migratory, pruritic erythematous serpiginous lesion observed intermittently until the parasite's death in the human, a dead-end host (picture 9). These infections are found worldwide in tropical and subtropical areas and commonly originate on sandy shores. ● The southern United States, Asia, Africa, Central America, and parts of eastern Europe are geographic foci for infection with the nematode Strongyloides stercoralis. (See "Strongyloidiasis".) Skin lesions are polyphasic early but may become maculopapular or urticarial in chronic infection. The classic and pathognomonic lesion of this helminthic infection is larva currens, a short-lived but recurrent pruritic, migratory, serpiginous rash involving the thighs or perineum. ● Travelers returning from Africa, Central America, and South America who develop painless subcutaneous nodules (usually on the head or bony prominences) or a pruritic dermatitis may have onchocerciasis, a nematode (Onchocerca volvulus) infection transmitted by the black fly (picture 10). (See "Onchocerciasis".) ● Travelers returning from the northeastern or southern African bush country, India, the Mediterranean, or Russia who present with a small (less than 1 cm) necrotic ulcer with surrounding erythema ("tache-noire") and subsequently develop fever, headache, regional http://www.uptodate.com/contents/fever-and-rash-in-the-immunocompetent-patient?topicKey=ID%2F2744&elapsedTimeMs=9&source=search_result&sear… 3/62

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lymphadenopathy, and a diffuse maculopapular skin rash may have Boutonneuse fever secondary to tick-associated Rick ettsia conorii infection. Similar presentations may be seen in travelers returning from eastern Australia who are infected with R. australis ("Queensland fever"), from northern Asia who are infected with R. sibirica ("North Asian fever"), or from Japan who are infected with R. japonica ("Oriental spotted fever"). Included in this group of "spotted fevers" is the mouse mite associated rickettsialpox caused by R. ak ari; it is seen in urban areas of the United States, Russia, and South Africa (see "Potential health hazards in travelers to Australia, New Zealand, and the southwestern Pacific (Oceania)" and "Rickettsialpox"). Scrub typhus, a potentially fatal rickettsial infection transmitted by mites, is characterized by a maculopapular rash, and in some patients, eschars. This entity can be seen in travelers to southeast Asia, the southern and western Pacific, Nepal, India, Korea, Australia, and China. (See "Scrub typhus: Clinical features and diagnosis".) ● Typhoid fever can occur in travelers to endemic areas like Mexico or India who ingest food or water contaminated by fecal matter. The skin manifestations are small, blanching papules called rose spots, usually found on the trunk, which typically arise in the second week of infection and fade within several days. (See "Epidemiology, microbiology, clinical manifestations, and diagnosis of typhoid fever".) Incubation period — Knowledge of the incubation period for infectious agents is particularly helpful to the physician trying to determine the significance of a rash in a patient exposed to another individual with a similar exanthem. A range of incubation periods exists for selected infectious agents that may be associated with fever and rash (table 1A-B). Exposure history — The category of exposures is a broad one in the differential diagnosis of fever and rash. Exposures to food, water, plant materials, animals, and infected human secretions can lead to rashes and can be associated with both occupational and nonoccupational contacts. As an example, the herpetic whitlow, seen in dental workers exposed to HSV-infected mucous membranes and secretions, is a classic occupation-associated infection (picture 11). Animal handlers, pet owners, and laboratory workers are more vulnerable to such infections, including [28-30]: ● Toxoplasmosis and cat scratch disease from cats and kittens (picture 12) (see "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease") ● Psittacosis from poultry, finches, or parrots (see "Psittacosis") ● Cryptococcosis from pigeon, dog, or cat feces ● Plague from goats, rabbits, dogs, squirrels, or coyotes (see "Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis infection)") ● Rat bite fever or leptospirosis from rats ● Tularemia in sheep handlers, wild game cooks, pelt dealers, and veterinarians, which can result in ulceroglandular, oculoglandular, glandular, oropharyngeal, typhoidal, or pneumonic syndromes [31] (picture 13) ● Pasteurella-associated wound infections secondary to cat and dog bites [32] Other environmental occupational exposures include: ● Papular or nodular lymphocutaneous lesions that develop on the extremities after trauma associated with an aquarium or swimming pool or after handling seafood are consistent with Mycobacterium marinum infections ("fish tank granuloma") [33,34]. ● Percutaneous injuries inflicted while handling the fish tilapia have been reported to cause Streptococcus iniae cellulitis of the hand [35]. ● Erysipelothrix rhusiopathiae, a gram-positive rod whose major host is swine, can produce a localized violaceous, cellulitic process involving primarily the hands or fingers in fish and meat handlers (picture 14). ● A gram-negative rod known as Edwardsiella tarda can cause fresh water–associated wound infections. Skin and soft tissue infections caused by this organism include abscesses, necrotizing fasciitis, bullae, myonecrosis, necrotizing fasciitis, and cellulitis [36]. ● Individuals who work with plants and soil (ie, florists, gardeners, farmers) are at risk for developing sporotrichosis, an infection of the extremities caused by the dimorphic fungus Sporothrix schenck ii (picture 15). (See "Clinical features and diagnosis of sporotrichosis".) A variety of conditions accompanied by fever and rash result from arthropod exposures. As examples, black flies are associated with onchocerciasis, deer flies with loiasis, fleas with plague and endemic typhus, mosquitoes with malaria, dengue fever, and chikungunya fever, assassin or reduviid bugs with Chagas disease, and sand flies with leishmaniasis. A report from the western United States described 15 patients with West Nile Virus fever who presented with a generalized maculopapular rash. A tingling and burning sensation was reported by four patients (27 percent) and pruritus by five patients (33 percent) [37]. The spirochete Borrelia burgdorferi is the etiologic agent of Lyme disease, an ixodid tick-associated infection seen in the United States. The classic skin lesion in this infection is erythema migrans (EM), a red expanding plaque-like lesion with central clearing that develops at the site of the tick bite (picture 16). (See "Clinical manifestations of Lyme disease in adults".) Other tick-borne diseases seen in the United States include: ● Ehrlichiosis can present as human monocytic ehrlichiosis (HME) caused by Ehrlichia chaffeensis or human granulocytic anaplasmosis (HGA) due to Anaplasma phagocytophilum [38]. Rash may or may not accompany ehrlichia infection which has also been termed "Spotless Rocky Mountain spotted fever" [39]. A rash is much more likely to be seen in cases of HME than HGE [40]. (See "Human ehrlichiosis and anaplasmosis".) ● Rick ettsia rick ettsii, the etiologic agent of RMSF, can be transmitted by the dog or wood tick and is primarily seen in the south-central and south Atlantic United States (see below). (See "Clinical manifestations and diagnosis of Rocky Mountain spotted fever".) ● Southern tick-associated rash illness (STARI), presumably caused by a spirochete carried by Amblyomma americanum ticks, is characterized by a flu-like illness and an erythema migrans–like rash. STARI should be considered in areas where A. americanum ticks are present, but where Lyme disease is absent or uncommon [41]. (See "Southern tick-associated rash illness (STARI)".) http://www.uptodate.com/contents/fever-and-rash-in-the-immunocompetent-patient?topicKey=ID%2F2744&elapsedTimeMs=9&source=search_result&sear… 4/62

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Recreational activities can result in infections associated with characteristic skin lesions. Exposure to hot tubs or whirlpools can cause Pseudomonas aeruginosa folliculitis (picture 17) [42]; whirlpool footbaths have also been associated with Mycobacterium fortuitum– associated furuncles in individuals who had pedicures [43]. Swimming in contaminated lake water has been associated with the development of hemolytic-uremic syndrome with thrombocytopenia-associated petechial skin lesions [44]. Herpes gladiatorum skin infections have been described in athletes who engage in contact sports like rugby and wrestling [45,46], and outbreaks of group A streptococcal and staphylococcal skin infections can occur in American and European football players after competition [47-49]. In one report, a cutaneous larva migrans infection secondary to Ancylostoma braziliense was observed in a beach volleyball player [50]. Medication history — Although drugs can cause a plethora of skin lesions, the relationship between drug fever and rash may not be as strong as many physicians believe. In one systematic analysis of 148 episodes of drug fever, fewer than 20 percent were associated with rash, and fewer than 50 percent of the rashes were urticarial in nature [51]. Hypersensitivity or allergic-type skin reactions (rash, itching, or hives) were evaluated in over 20,000 hospitalized patients in the Boston Collaborative Drug surveillance program, and though associated fever was not evaluated, only about 2 percent of patients receiving drugs developed cutaneous reactions [52]. Antibiotics such as penicillins, cephalosporins, and trimethoprim-sulfamethoxazole were associated with high rates of allergic skin reactions. Other drugs classically associated with fever and hypersensitivity reactions include barbiturates, phenytoin, procainamide, and quinidine. However, only one in every 1000 hospitalized patients develops a severe cutaneous drug reaction like Stevens-Johnson syndrome or toxic epidermal necrolysis [53]. A metabolic predisposition leading to ineffective detoxification of sulfonamide and anticonvulsant metabolites may lead to severe adverse cutaneous drug reactions [54]. These reactions typically develop one to three weeks after the initiation of the culprit agent [55]. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".) Immunization history — Inadequately immunized individuals are susceptible to the traditional childhood viral infections and serve as an often overlooked reservoir of disease. The current recommended immunizations for children in the United States include hepatitis A and B, diphtheria and tetanus toxoids and pertussis, Haemophilus influenzae type b, rotavirus, poliovirus, measles-mumps-rubella (MMR), varicella, influenza, human papillomavirus, pneumococcus, and meningococcus (in adolescents). Follow-up of older children with their primary care physicians provides an opportune time for confirming appropriate immunizations. (See "Standard immunizations for children and adolescents".) Similarly, zoster vaccination is recommended for adults 60 years of age and older to decrease the incidence of zoster and postherpetic neuralgia. (See "Prevention of varicella-zoster virus infection: Herpes zoster", section on 'The use of zoster vaccine'.) Sexual history — A thorough sexual history is essential in evaluating the patient with a rash of unknown etiology. Genital or rectal ulcerations may be caused by a variety of infectious agents, including syphilis (picture 18), herpes simplex (picture 19), lymphogranuloma venereum (picture 20), chancroid (picture 21), and donovanosis (picture 22 and table 2A-B). These infections may not be associated with fever. Syphilis can have a variety of cutaneous manifestations. The primary stage is characterized by the chancre, a painless, often solitary, indurated genital ulceration with elevated, well-defined borders. The skin lesions of secondary syphilis include a generalized papular or maculopapular rash (rarely pustular) that also affects the palms and soles (picture 23). Other lesions seen during this stage include condylomata lata, flat moist condylomata-like lesions that are gray, infectious, and located around the genitals, mouth, anus, and other moist areas (picture 24). Approximately 15 to 30 percent of infected patients will manifest mucous membrane ulcerations that are sharply demarcated and covered with a gray exudate, (ie, mucous patches). Patchy alopecia resulting in a "moth-eaten" appearance of the scalp can also be seen during this stage. (See "Pathophysiology, transmission, and natural history of syphilis".) Classic skin lesions of late, or tertiary, syphilis include the gumma, generally a solitary granulomatous subcutaneous skin or mucous membrane lesion that is initially nodular before ulcerating. Enlargement of these lesions can result in local tissue destruction. Also seen in tertiary syphilis are noduloulcerative lesions arranged in characteristic ring-like patterns known as lues maligna (picture 25). Resolution of these lesions results in hyperpigmented scars. Disseminated gonococcal infection causes a rash in as many as 90 percent of patients. The rash consists of fewer than 20 to 30 papular, nodular, and/or petechial lesions that develop a vesiculopustular component and then, finally, a necrotic, hemorrhagic appearance [56]. The rash contains lesions that, like those of primary varicella infection, are in different stages of evolution. (See "Disseminated gonococcal infection".) The acute retroviral syndrome that occurs approximately two to six weeks after primary human immunodeficiency syndrome (HIV) infection is characterized by fever, sore throat, malaise, headache, lymphadenopathy, mucocutaneous ulceration, and rash. The rash, seen in more than 50 percent of patients, is usually transient, maculopapular, nonpruritic, and truncal or facial in location [57]. This presentation can often be confused for infectious mononucleosis [58]. (See "Acute and early HIV infection: Pathogenesis and epidemiology".) Immunocompetence of the host — The possible etiologies of fever and rash are quite different if the host is immunosuppressed. Thus, determining the underlying immunologic status of the host is essential in assessing any patient with fever and rash [59]. DIAGNOSTIC APPROACH — The diagnostic approach to the patient with fever and rash should focus on the appearance of the rash in addition to the detailed epidemiologic history listed above. Characteristics of the rash — A history of the rash should include the following questions [5]: ● Was a prodrome present? ● Where and when did the rash start? ● How has the rash progressed anatomically? ● Has the rash changed in appearance? ● Has any treatment been instituted for the rash? http://www.uptodate.com/contents/fever-and-rash-in-the-immunocompetent-patient?topicKey=ID%2F2744&elapsedTimeMs=9&source=search_result&sear… 5/62

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In examining a rash, it is essential to characterize the lesions, both individually and collectively, according to morphology and arrangement (annular, linear, serpiginous, dermatomal, etc), distribution (isolated versus generalized, bilateral versus unilateral, symmetric, occurring on exposed areas, etc), and evolution (centrifugal versus centripetal) [5,60]. In addition, a differential diagnosis for fever and rash can be based upon the appearance of the rash and its accompanying signs (table 3A-C and table 4A-B). The following definitions are useful in interpreting the tables and characterizing lesions and rashes [61]: ● Macule – Nonpalpable, circumscribed lesion that is flat and less than 1 cm in diameter ● Papule – Palpable lesion that is solid, elevated, and less than 1 cm in diameter ● Maculopapular – Confluent, erythematous rash made up of both macular and papular lesions ● Purpura – Papular or macular nonblanching lesions that are due to extravasation of red blood cells ● Nodule – Deep-seated, roundish lesion less than 1.5 cm in diameter that can involve the epidermal, dermal, and/or subcutaneous tissue ● Plaque – A palpable elevated lesion greater than 1 cm in diameter ● Vesicle – A distinct, elevated skin lesion that contains fluid and is less than 1 cm in diameter ● Bulla – A vesicle that is more than 1 cm in diameter ● Pustule – A vesicle that contains pus ● Ulcer – Loss of the epidermis and upper layer of the dermis, resulting in a depressed skin lesion While these categories are useful and descriptive, many rashes have overlapping features, and a number of infectious agents can present with several different rash morphologies. Different infectious agents can also produce similar types of rashes. Several skin conditions can be identified based upon appearance but can be caused by a variety of infectious and noninfectious etiologies. ● Erythema multiforme – Symmetrically distributed "target" lesions that typically involve the palms, soles, and mucous membranes, reflecting epidermal and dermal involvement (picture 26 and table 5) (see "Pathogenesis, clinical features, and diagnosis of erythema multiforme") ● Erythema nodosum – Painful red nodular lesions usually found symmetrically on the lower extremities and representing inflammation in the panniculus (picture 27) (see "Erythema nodosum") ● Toxic epidermal necrolysis – A severe skin and mucosal disorder that manifests initially as tender widespread erythema with subsequent loss of the epidermis, usually due to drugs such as sulfonamides, allopurinol, nonsteroidal antiinflammatory drugs, and anticonvulsants (picture 28 and table 6) ● Urticaria – A skin condition associated with the presence of transient wheals (ie, papules or plaques) due to dermal edema, with no evidence of epidermal involvement or abnormality (picture 29 and table 7) (see "New onset urticaria") Enanthems are mucous membrane lesions often associated with exanthems in systemic infectious diseases. Examples include oral or genital mucous patches (secondary syphilis), oral gummatous lesions (tertiary syphilis), oral ulcers (disseminated histoplasmosis, gonococcus, or tuberculosis), palatal petechial lesions (rubella and EBV mononucleosis), oral vesicular lesions (Coxsackie-associated hand, foot, and mouth syndrome, varicella, and primary HSV), and strawberry tongue (scarlet fever, Kawasaki syndrome, toxic shock syndrome). Koplik's spots, the tiny punctate elevated white buccal mucosa lesions located adjacent to the lower molars, are pathognomonic of measles and can precede the rash by 24 to 48 hours. Physical examination — A thorough physical examination should focus on the following [5]: ● Vital signs ● General appearance to assess the severity of illness ● Strict attention to lymph nodes, mucous membranes, conjunctivae, and genitalia ● Meningeal signs and complete neurologic evaluation ● Liver and spleen size ● Joint examination ● Skin examination (table 3A-C and table 4A-B). Laboratory testing — Appropriate laboratory testing includes [5]: ● Nonspecific tests such as complete blood count and urinalysis ● Blood cultures, including specific media and isolation methods for work-up of bacteria, mycobacterial, and fungal organisms should be inoculated prior to beginning antimicrobial therapy ● Serologic tests, when appropriate (eg, for Coccidioides immitis, hepatitis B, Toxoplasma gondii, Borrelia burgdorferi, Treponema pallidum, dengue fever, and HIV) ● Antigen tests, when appropriate (eg, serum cryptococcal antigen) Fluid from vesicular, pustular, petechial, ulcerative, and bullous lesions can be examined. Vesicular lesions should be unroofed so that the base of the lesion can be swabbed; herpes simplex virus and varicella-zoster virus can be distinguished with rapid fluorescent antibody studies. Viral culture can also be performed. Aspirated fluid from pustules and bullous lesions should be Gram stained and cultured in an expeditious fashion by the microbiology laboratory. In suspected cases of syphilis, exudative material from the ulcer base can be examined by darkfield microscopy. (See "Diagnostic testing for syphilis".) Skin biopsy can be particularly useful in establishing a diagnosis for nodular lesions but can also be obtained for petechial-purpuric, maculopapular, and ulcerative rashes. Aseptically obtained biopsy material should be sent to the microbiology and pathology laboratories for appropriate culture and histopathologic evaluation. In suspected cases of Rocky Mountain spotted fever, direct immunofluorescent demonstration of rickettsial organisms is diagnostic. (See "Clinical manifestations and diagnosis of Rocky Mountain spotted fever".) http://www.uptodate.com/contents/fever-and-rash-in-the-immunocompetent-patient?topicKey=ID%2F2744&elapsedTimeMs=9&source=search_result&sear… 6/62

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SELECTED FEVER AND RASH EMERGENCIES — Several infections associated with fever and rash constitute emergencies that must be recognized promptly by the evaluating clinician. Meningococcal infection — The gram-negative diplococcus N. meningitidis can cause life-threatening infection in children and young adults; outbreaks of infection can occur, especially among groups with confined living conditions, such as military bases, day care centers, and dormitories. The infection can also develop in individuals with congenital late terminal complement deficiency, acquired complement deficiency (ie, nephrotic syndrome, systemic lupus erythematosus), and splenectomy. (See "Epidemiology of Neisseria meningitidis infection".) Meningococcal infection can result in a number of different clinical presentations, but meningococcemia and/or meningitis are the most common. In addition to fever, myalgia, somnolence, headache, and nausea, rash occurs in most patients with meningococcemia. Early lesions may be macular, but rapidly increasing numbers of petechial or purpuric lesions can develop on the distal extremities and trunk, usually sparing the palms and soles (in contrast to RMSF) (picture 30). An urticarial rash can also be seen [62]. Lesions on mucosal surfaces are also common. (See "Clinical manifestations of meningococcal infection".) In one review of 151 patients with meningococcal infection, 75 percent had petechial/maculopapular lesions, 11 percent purpuric/ecchymotic lesions, and 14 percent no skin lesions [63]. Mortality was considerably higher in those with purpuric/ecchymotic lesions. Meningococcemia may be rapidly fatal, with mortality rates of approximately 10 to 25 percent. Prompt recognition, supportive therapy to maintain adequate blood pressure and oxygenation, and pathogen-directed therapy with parenteral antibiotics (usually high doses of penicillin or a third-generation cephalosporin) are essential. Purpura fulminans, a particularly severe complication of meningococcemia, refers to the fulminant hemorrhagic skin necrosis that can be seen in association with disseminated intravascular coagulation (DIC) and shock. (See "Treatment and prevention of meningococcal infection".) Bacterial endocarditis — Skin lesions may offer a clue to the underlying diagnosis of infective endocarditis (IE). Associated peripheral cutaneous or mucocutaneous lesions include petechiae, splinter hemorrhages, Janeway lesions, Osler's nodes, and Roth spots. (See "Clinical manifestations and diagnosis of infective endocarditis" and "Infective endocarditis: Historical and Duke criteria".) Petechiae are not specific for infective endocarditis but are its most common skin manifestation. They may be present on the skin, usually on the extremities, or on mucous membranes such as the palate or conjunctivae, the latter usually as hemorrhages best seen with eversion of either upper or lower eyelids (picture 31). Splinter hemorrhages, also nonspecific for endocarditis, are nonblanching, linear reddish-brown lesions found under the nail bed (picture 32). Janeway lesions, Osler's nodes, and Roth spots are more specific for IE but also less common; Roth spots are particularly rare. Janeway lesions are macular, nonblanching, nonpainful, and erythematous lesions on the palms and soles (picture 33). By contrast, Osler's nodes are painful, violaceous nodules found in the pulp of fingers and toes and are seen more often in subacute than acute cases of IE (picture 34). Roth spots are exudative, edematous hemorrhagic lesions of the retina. Of note, conjunctival hemorrhage, Janeway lesions, Osler's nodes, and Roth spots are included as minor criteria in the Duke criteria for the diagnosis of infective endocarditis [64]. It is important to recognize the skin manifestations of endocarditis in order to obtain blood cultures and initiate appropriate therapy. A prospective cohort study reported that S. aureus is the most common cause of infective endocarditis in many locations worldwide [65]. Despite improvements in therapy and the availability of surgical intervention, there is still an appreciable mortality rate of 25 to 40 percent for patients with S. aureus IE who are not injection drug users [66]. (See "Clinical manifestations of Staphylococcus aureus infection".) Significantly, the incidence of infective endocarditis has remained unchanged in the last 20 years [67]. Rocky Mountain spotted fever — Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by Rick ettsia rick ettsii. After an incubation period of as little as two days, fever, headache, malaise, conjunctival suffusion, and myalgia usually develop. In most patients, a rash appears within the following week, initially on the wrists and ankles and later on the palms and soles, before spreading centripetally to include the arms, legs, face, and trunk. The differential diagnosis includes meningococcemia, infective endocarditis, measles, secondary syphilis, and other rickettsial diseases. The rash is at first erythematous and maculopapular. Progression to a petechial rash is often noted and, in severe cases of RMSF, purpura and hemorrhagic necrosis can occur (picture 35). Associated thrombocytopenia can make the diagnosis of RMSF difficult to distinguish from meningococcemia. However, several clinical clues favor the diagnosis of RMSF, including a history of tick bite or visits to areas where RMSFassociated ticks are present, occurrence of the rash a median of three to four days following the onset of fever, relative leukopenia, and elevated aminotransferases. (See "Clinical manifestations and diagnosis of Rocky Mountain spotted fever".) Toxic shock syndrome — Initially used in the late 1970s to describe a disease syndrome in children infected with S. aureus, toxic shock syndrome (TSS) became a well-known entity in the early 1980s when its association with young menstruating women and tampon use was described [68-70]. Nonmenstrual toxic shock syndrome has been associated with surgical wounds, burns, skin ulcerations, catheters, and nasal packings. (See "Staphylococcal toxic shock syndrome".) Criteria for the diagnosis of TSS include a temperature above 38.9ºC, hypotension, a desquamating rash, involvement of at least three organ systems, and exclusion of clinical mimics such as RMSF, leptospirosis, and measles [71]. Multiple toxins have been described in association with this syndrome, particularly TSS toxin (TSST-1) in menstrual-associated TSS [72]. The rash seen in TSS is diffuse and erythematous and can resemble a sunburn (picture 36). The conjunctivae are also often involved (picture 37). Fever, diarrhea, muscle aches, and nausea/emesis are commonly present. Desquamation, usually of the palms and soles or at the sites of the original rash, is classically described one to three weeks later. Group A streptococci (GAS) can also produce a toxic shock–like syndrome, most often in association with a skin or soft tissue infection. (See "Epidemiology, clinical manifestations, and diagnosis of streptococcal toxic shock syndrome".) Streptococcal pyrogenic exotoxins that cause cytokine production, analogous to staphylococcal TSST-1, appear to be responsible for http://www.uptodate.com/contents/fever-and-rash-in-the-immunocompetent-patient?topicKey=ID%2F2744&elapsedTimeMs=9&source=search_result&sear… 7/62

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initiating this syndrome. Several general differences are noted between TSS caused by GAS and by S. aureus. In GAS TSS, mortality is higher (30 versus 3 percent with S. aureus), bacteremia and tissue necrosis are more common, and generalized erythema is less common [71]. (See "Treatment of streptococcal toxic shock syndrome".) INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.) ● Basics topics (see "Patient information: Scarlet fever (The Basics)" and "Patient information: When to worry about a fever (The Basics)") SUMMARY ● Fever with an accompanying rash is a common symptom constellation in patients presenting to clinicians' offices and emergency departments. Skin manifestations may provide the only early clue to an underlying infection, may be the hallmark of contagious disease, and/or may be an early sign of a life-threatening infection. The differential diagnosis of fever and rash is extremely broad, but this symptom complex provides an opportunity for the diligent clinician to establish a probable etiology through a careful history and physical examination. (See 'Introduction' above.) ● A systematic approach is crucial for establishing a timely diagnosis, determining early therapy when appropriate, and considering isolation of the patient if necessary. Epidemiologic clues are important to pursue such as: • Age of the patient • Season of the year • Travel history • Geographic location • Exposures including to insects, animals, and ill contacts • Medications • Immunizations and history of childhood illnesses • The immune status of the host (See 'Introduction' above.) ● Features of the rash are also important to consider, including: • Characteristics of the lesions • Distribution and progression of the rash • Timing of the onset in relation to fever • Change in morphology, such as papules to vesicles or petechiae (See 'Introduction' above.) ● A number of infections characterized by fever and rash have a distinct seasonal predisposition. As examples, nonpolio enteroviral infections occur in the summer and fall months; Kawasaki syndrome, meningococcal infection, and parvoviral infections present most commonly in the winter or early spring months; measles and rubella are more frequent in the spring; tick-borne diseases such as Lyme disease, ehrlichiosis, and Rocky Mountain spotted fever (RMSF) primarily occur in the spring and summer; tularemia and plague are usually seen in the summer. (See 'Season of the year' above.) ● Exposures to food, water, plant materials, animals, and infected human secretions can lead to rashes and can be associated with both occupational and nonoccupational contacts. (See 'Exposure history' above.) ● A thorough sexual history is essential in evaluating the patient with a rash of unknown etiology. Genital or rectal ulcerations may be caused by a variety of infectious agents, including syphilis (picture 18), herpes simplex (picture 19), lymphogranuloma venereum (picture 20), chancroid (picture 21), and donovanosis (picture 22 and table 2A-B). (See 'Sexual history' above.) ● The diagnostic approach to the patient with fever and rash should focus on the appearance of the rash in addition to the detailed epidemiologic history listed above. (See 'Diagnostic approach' above.) ● A history of the rash should include the following questions: • Was a prodrome present? • Where and when did the rash start? • How has the rash progressed anatomically? • Has the rash changed in appearance? • Has any treatment been instituted for the rash? (See 'Characteristics of the rash' above.) http://www.uptodate.com/contents/fever-and-rash-in-the-immunocompetent-patient?topicKey=ID%2F2744&elapsedTimeMs=9&source=search_result&sear… 8/62

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● In examining a rash, it is essential to characterize the lesions, both individually and collectively, according to morphology and arrangement (annular, linear, serpiginous, dermatomal, etc), distribution (isolated versus generalized, bilateral versus unilateral, symmetric, occurring on exposed areas, etc), and evolution (centrifugal versus centripetal). In addition, a differential diagnosis for fever and rash can be based upon the appearance of the rash and its accompanying signs (table 3A-C and table 4A-B). (See 'Characteristics of the rash' above.) ● Appropriate laboratory testing includes: • Nonspecific tests such as complete blood count and urinalysis • Blood cultures, including specific media and isolation methods for work-up of bacteria, mycobacterial, and fungal organisms should be inoculated prior to beginning antimicrobial therapy • Serologic tests, when appropriate (eg, for Coccidioides immitis, hepatitis B, Toxoplasma gondii, Borrelia burgdorferi, Treponema pallidum, dengue fever, and HIV). • Antigen tests, when appropriate (eg, serum cryptococcal antigen) (see 'Laboratory testing' above) ● Fluid from vesicular, pustular, petechial, ulcerative, and bullous lesions can be examined. Vesicular lesions should be unroofed so that the base of the lesion can be swabbed; herpes simplex virus and varicella-zoster virus can be distinguished with rapid fluorescent antibody studies. Viral culture can also be performed. Aspirated fluid from pustules and bullous lesions should be Gram stained and cultured by the microbiology laboratory. (See 'Laboratory testing' above.) ● Skin biopsy can be particularly useful in establishing a diagnosis for nodular lesions but can also be obtained for petechial-purpuric, maculopapular, and ulcerative rashes. Biopsy material should be sent to the microbiology and pathology laboratories for appropriate culture and histopathologic evaluation. (See 'Laboratory testing' above.) ● Several infections associated with fever and rash constitute emergencies that must be recognized promptly by the evaluating clinician. Such infections include meningococcal infection, bacterial endocarditis, Rocky Mountain spotted fever, and toxic shock syndrome. (See 'Selected fever and rash emergencies' above.) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Levin S, Goodman LJ. An approach to acute fever and rash (AFR) in the adult. In: Current Clinical Topics in Infectious Diseases, Remington JS, Swartz MN (Eds), Blackwell Science, Boston 1995. p.19. 2. Weber DJ, Cohen MS. The acutely ill patient with fever and rash. In: Principles and Practices of Infectious Diseases, Mandell GL, Douglas RG Jr, Bennett JE (Eds), Churchill Livingstone, New York City 1995. p.549. 3. Valdez, LM, Septimus, EJ. Clinical approach to rash and fever. Infect Dis Pract 1996; 20:1. 4. Sumaya CV. Acute exanthematous disease. In: Infectious Diseases of Children and Adults. A Step-by-Step Approach to Diagnosis and Treatment, Pickering LK, DuPont HL (Eds), Addison-Wesley, Menlo Park, CA 1986. p.167. 5. Sanders CV. Approach to the diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams and Wilkins, Baltimore 1995. p.296. 6. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 2005; 41:1373. 7. Falagas ME, Vergidis PI. Narrative review: diseases that masquerade as infectious cellulitis. Ann Intern Med 2005; 142:47. 8. Cherry JD. Contemporary infectious exanthems. Clin Infect Dis 1993; 16:199. 9. Rauch AM, Hurwitz ES. Centers for Disease Control (CDC) case definition for Kawasaki syndrome. Pediatr Infect Dis 1985; 4:702. 10. Mackenzie A, Fuite LA, Chan FT, et al. Incidence and pathogenicity of Arcanobacterium haemolyticum during a 2-year study in Ottawa. Clin Infect Dis 1995; 21:177. 11. Sugerman DE, Barskey AE, Delea MG, et al. Measles outbreak in a highly vaccinated population, San Diego, 2008: role of the intentionally undervaccinated. Pediatrics 2010; 125:747. 12. Andiman WA. The Epstein-Barr virus and EB virus infections in childhood. J Pediatr 1979; 95:171. 13. Anderson LJ. Role of parvovirus B19 in human disease. Pediatr Infect Dis J 1987; 6:711. 14. Blake PA, Merson MH, Weaver RE, et al. Disease caused by a marine Vibrio. Clinical characteristics and epidemiology. N Engl J Med 1979; 300:1. 15. Centers for Disease Control and Prevention (CDC). Vibrio illnesses after Hurricane Katrina--multiple states, August-September 2005. MMWR Morb Mortal Wkly Rep 2005; 54:928. 16. Suh KN, Kozarsky PE, Keystone JS. Evaluation of fever in the returned traveler. Med Clin North Am 1999; 83:997. 17. Lupi O, Tyring SK. Tropical dermatology: viral tropical diseases. J Am Acad Dermatol 2003; 49:979. 18. O'Brien D, Tobin S, Brown GV, Torresi J. Fever in returned travelers: review of hospital admissions for a 3-year period. Clin Infect Dis 2001; 33:603. 19. Lockwood DN, Keystone JS. Skin problems in returning travelers. Med Clin North Am 1992; 76:1393. 20. Mackey SL, Wagner KF. Dermatologic manifestations of parasitic diseases. Infect Dis Clin North Am 1994; 8:713. 21. Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med 2006; 354:119. http://www.uptodate.com/contents/fever-and-rash-in-the-immunocompetent-patient?topicKey=ID%2F2744&elapsedTimeMs=9&source=search_result&sear… 9/62

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22. Speil C, Mushtaq A, Adamski A, Khardori N. Fever of unknown origin in the returning traveler. Infect Dis Clin North Am 2007; 21:1091. 23. McHugh CP, Melby PC, LaFon SG. Leishmaniasis in Texas: epidemiology and clinical aspects of human cases. Am J Trop Med Hyg 1996; 55:547. 24. Centers for Disease Control and Prevention (CDC). Locally acquired Dengue--Key West, Florida, 2009-2010. MMWR Morb Mortal Wkly Rep 2010; 59:577. 25. Rigau-Pérez JG, Clark GG, Gubler DJ, et al. Dengue and dengue haemorrhagic fever. Lancet 1998; 352:971. 26. Taubitz W, Cramer JP, Kapaun A, et al. Chikungunya fever in travelers: clinical presentation and course. Clin Infect Dis 2007; 45:e1. 27. Riyaz N, Riyaz A, Rahima, et al. Cutaneous manifestations of chikungunya during a recent epidemic in Calicut, north Kerala, south India. Indian J Dermatol Venereol Leprol 2010; 76:671. 28. Goldstein EJ. Household pets and human infections. Infect Dis Clin North Am 1991; 5:117. 29. Fox JG, Lipman NS. Infections transmitted by large and small laboratory animals. Infect Dis Clin North Am 1991; 5:131. 30. Hankenson FC, Johnston NA, Weigler BJ, Di Giacomo RF. Zoonoses of occupational health importance in contemporary laboratory animal research. Comp Med 2003; 53:579. 31. Craven RB, Barnes AM. Plague and tularemia. Infect Dis Clin North Am 1991; 5:165. 32. Talan DA, Citron DM, Abrahamian FM, et al. Bacteriologic analysis of infected dog and cat bites. Emergency Medicine Animal Bite Infection Study Group. N Engl J Med 1999; 340:85. 33. Edelstein H. Mycobacterium marinum skin infections. Report of 31 cases and review of the literature. Arch Intern Med 1994; 154:1359. 34. Aubry A, Chosidow O, Caumes E, et al. Sixty-three cases of Mycobacterium marinum infection: clinical features, treatment, and antibiotic susceptibility of causative isolates. Arch Intern Med 2002; 162:1746. 35. Weinstein MR, Litt M, Kertesz DA, et al. Invasive infections due to a fish pathogen, Streptococcus iniae. S. iniae Study Group. N Engl J Med 1997; 337:589. 36. Slaven EM, Lopez FA, Hart SM, Sanders CV. Myonecrosis caused by Edwardsiella tarda: a case report and case series of extraintestinal E. tarda infections. Clin Infect Dis 2001; 32:1430. 37. Ferguson DD, Gershman K, LeBailly A, Petersen LR. Characteristics of the rash associated with West Nile virus fever. Clin Infect Dis 2005; 41:1204. 38. Dumler JS. Is human granulocytic ehrlichiosis a new Lyme disease? Review and comparison of clinical, laboratory, epidemiological, and some biological features. Clin Infect Dis 1997; 25 Suppl 1:S43. 39. Bakken JS, Krueth J, Wilson-Nordskog C, et al. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA 1996; 275:199. 40. Fishbein DB, Dawson JE, Robinson LE. Human ehrlichiosis in the United States, 1985 to 1990. Ann Intern Med 1994; 120:736. 41. Masters EJ, Grigery CN, Masters RW. STARI, or Masters disease: Lone Star tick-vectored Lyme-like illness. Infect Dis Clin North Am 2008; 22:361. 42. Silverman AR, Nieland ML. Hot tub dermatitis: a familial outbreak of Pseudomonas folliculitis. J Am Acad Dermatol 1983; 8:153. 43. Winthrop KL, Abrams M, Yakrus M, et al. An outbreak of mycobacterial furunculosis associated with footbaths at a nail salon. N Engl J Med 2002; 346:1366. 44. Keene WE, McAnulty JM, Hoesly FC, et al. A swimming-associated outbreak of hemorrhagic colitis caused by Escherichia coli O157:H7 and Shigella sonnei. N Engl J Med 1994; 331:579. 45. Becker TM, Kodsi R, Bailey P, et al. Grappling with herpes: herpes gladiatorum. Am J Sports Med 1988; 16:665. 46. White WB, Grant-Kels JM. Transmission of herpes simplex virus type 1 infection in rugby players. JAMA 1984; 252:533. 47. Falck G. Group A streptococcal skin infections after indoor association football tournament. Lancet 1996; 347:840. 48. Glezen WP, Lindsay RL, DeWalt JL, Dillon HC Jr. Epidemic pyoderma caused by nephritogenic streptococci in college athletes. Lancet 1972; 1:301. 49. Kazakova SV, Hageman JC, Matava M, et al. A clone of methicillin-resistant Staphylococcus aureus among professional football players. N Engl J Med 2005; 352:468. 50. Biolcati G, Alabiso A. Creeping eruption of larva migrans--a case report in a beach volley athlete. Int J Sports Med 1997; 18:612. 51. Mackowiak PA, LeMaistre CF. Drug fever: a critical appraisal of conventional concepts. An analysis of 51 episodes in two Dallas hospitals and 97 episodes reported in the English literature. Ann Intern Med 1987; 106:728. 52. Arndt KA, Jick H. Rates of cutaneous reactions to drugs. A report from the Boston Collaborative Drug Surveillance Program. JAMA 1976; 235:918. 53. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994; 331:1272. 54. Wolkenstein P, Charue D, Laurent P, et al. Metabolic predisposition to cutaneous adverse drug reactions. Role in toxic epidermal necrolysis caused by sulfonamides and anticonvulsants. Arch Dermatol 1995; 131:544. 55. Wolkenstein P, Revuz J. Toxic epidermal necrolysis. Dermatol Clin 2000; 18:485. 56. Koss PG. Disseminated gonococcal infection. The tenosynovitis-dermatitis and suppurative arthritis syndromes. Cleve Clin Q 1985; 52:161. 57. de Jong MD, Hulsebosch HJ, Lange JM. Clinical, virological and immunological features of primary HIV-1 infection. Genitourin Med 1991; 67:367. 58. Vanhems P, Allard R, Cooper DA, et al. Acute human immunodeficiency virus type 1 disease as a mononucleosis-like illness: is the diagnosis too restrictive? Clin Infect Dis 1997; 24:965. 59. Lopez FA, Sanders CV. Dermatologic infections in the immunocompromised (non-HIV) host. Infect Dis Clin North Am 2001; 15:671. 60. Nesbitt LT Jr. Evaluating the patient with a skin infection: General considerations. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995. p.1. http://www.uptodate.com/contents/fever-and-rash-in-the-immunocompetent-patient?topicKey=ID%2F2744&elapsedTimeMs=9&source=search_result&se…

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61. Glossary. In: Dermatologic Manifestations of Infectious Diseases, Peterson PK, Dahl MV (Eds), The Upjohn Company, Kalamazoo, Michigan 1982. p.4. 62. Ferguson LE, Hormann MD, Parks DK, Yetman RJ. Neisseria meningitidis: presentation, treatment, and prevention. J Pediatr Health Care 2002; 16:119. 63. Toews WH, Bass JW. Skin manifestations of meningococcal infection; an immediate indicator of prognosis. Am J Dis Child 1974; 127:173. 64. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 1994; 96:200. 65. Murdoch DR, Corey GR, Hoen B, et al. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Arch Intern Med 2009; 169:463. 66. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 2005; 111:e394. 67. Moreillon P, Que YA. Infective endocarditis. Lancet 2004; 363:139. 68. Todd J, Fishaut M, Kapral F, Welch T. Toxic-shock syndrome associated with phage-group-I Staphylococci. Lancet 1978; 2:1116. 69. Davis JP, Chesney PJ, Wand PJ, LaVenture M. Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention. N Engl J Med 1980; 303:1429. 70. Shands KN, Schmid GP, Dan BB, et al. Toxic-shock syndrome in menstruating women: association with tampon use and Staphylococcus aureus and clinical features in 52 cases. N Engl J Med 1980; 303:1436. 71. Stevens DL. The toxic shock syndromes. Infect Dis Clin North Am 1996; 10:727. 72. Schlievert PM, Shands KN, Dan BB, et al. Identification and characterization of an exotoxin from Staphylococcus aureus associated with toxic-shock syndrome. J Infect Dis 1981; 143:509. Topic 2744 Version 12.0

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GRAPHICS Measles exanthem

Blanching erythematous rash with some confluent areas on the trunk in a patient with measles. Copyright Dr. Michael Bennish; reproduced with his permission. Graphic 57093 Version 3.0

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Primary varicella lesions

Vesicular lesions on an erythematous base are characteristic of chickenpox. The lesions occur in crops and are present in a variety of stages from maculopapular to vesicular or even pustular. Central necrosis and early crusting is also visible. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995.

http://www.lww.com Graphic 55533 Version 5.0

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Erythema infectiosum

Reticulating pattern of an erythematous eruption on the extremities due to parvorvirus B19. Rash is more common in children. The presence of intense erythema (a slapped cheek appearance) on the face is highly characteristic. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 75125 Version 5.0

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Strawberry tongue

Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc. Graphic 68321 Version 3.0

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Rash in infectious mononucleosis

A generalized, erythematous, maculopapular eruption is often seen in patients with infectious mononucleosis after the administration of ampicillin. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 57224 Version 5.0

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Dermatomal herpes zoster

Grouped vesicles on an erythematous base present in a dermatomal distribution on the upper back due to Herpes zoster. The lesions stop abruptly at the midline. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 79886 Version 3.0

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Cutaneous leishmaniasis

Nodular lesion with central ulceration found on the arm of a patient with cutaneous leishmaniasis. Fever is typically absent and a history of travel can usually be obtained. Courtesy of Charles V Sanders. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 71944 Version 3.0

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Romaña’s sign

Unilateral eyelid edema is the Romaña's sign of Trypanosoma cruzi infection. This agent causes Chagas' disease and is found in Central and South America. Courtesy of Joy D Jester, Rolando E Saenz, Lee T Nesbitt, Jr, and WA Krotoski. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 58601 Version 8.0

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Skin lesion of cutaneous larva migrans

Characteristic elevated, serpiginous, reddish-brown lesion of cutaneous larva migrans as the larvae migrate at a rate of several millimeters per day. Courtesy of Peter F Weller, MD. Graphic 60144 Version 1.0

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Onchocerciasis

A painless subcutaneous nodule (arrow) inhabited by the adult filarilal worms of Onchocerca volvulus which is transmitted by the black fly. The female adult worms give rise to the microfilariae that produce the dermal and ocular manifestations of onchocerciasis. Courtesy of Krotoski WA. The Skin and Infection: A Color Atlas and Text, Sanders, CV, Nesbitt, LT Jr (Eds), Williams &Wilkins, Baltimore 1995.

http://www.lww.com Graphic 59106 Version 5.0

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Incubation period for infectious diseases associated with fever and rash Agent/disease

Incubation period

Arcanobacterium haemolyticum

Unknown

Atypical measles

7 to 14 days

Blastomyces dermatitidis

30 to 45 days

Boutonneuse fever (Rickettsia conorii)

6 to 10 days

Cat scratch disease

7 to 14 days

Chancroid

1 to 35 days

Chickenpox

10 to 20 days

Chlamydia psittaci

5 to 21 days

Coccidioides immitis

7 to 21 days

Coxsackie/echovirus

2 to 9 days

Cutaneous larva migrans

2 to 4 days

Dengue

3 to 14 days

Disseminated gonococcal infection

5 days to several months

Ehrlichiosis

7 to 21 days

Escherichia coli 0157:H7

3 to 8 days

Epstein-Barr virus (mononucleosis)

30 to 50 days

Gnathostomiasis

3 to 12 months

Granuloma inguinale

8 to 80 days

Hepatitis B

45 to 160 days

Hepatitis C

14 to 180 days

Herpes simplex (genital)

2 to 7 days

Human immunodeficiency virus (HIV)

28 to 180 days

Kawasaki syndrome

Unknown

Leishmaniasis

14 to 56 days

Loiasis

6 to 12 months

Lyme disease

3 to 30 days

Lymphogranuloma venerum (LGV)

3 to 21 days

Mycobacterium leprae

>1 year

Mycobacterium marinum

14 to 56 days

Adapted with permission from Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. Graphic 66762 Version 3.0

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Incubation period for infectious diseases associated with fever and rash Agent/disease

Incubation period

Mycoplasma pneumoniae

7 to 28 days

Neisseria meningitidis

1 to 10 days

Onchocerciasis

6 to 12 months

Parvovirus B19

7 to 21 days

Reiter's syndrome

7 to 14 days

Relapsing fever

4 to 18 days

Rheumatic fever

7 to 35 days

Rickettsialpox, Rickettsia akari

10 to 14 days

Rocky Mountain spotted fever, Rickettsia rickettsii

2 to 14 days

Roseola infantum

5 to 15 days

Rubella

5 to 21 days

Rubeola

10 to 14 days

Salmonella typhi (enteric fever)

3 to 60 days

Spirillum minus

7 to 24 days

Sporothrix schenckii

7 to 30 days

Staphylococcal toxic shock syndrome

2 days

Streptobacillus moniliformis

3 to 22 days

Syphilis

9 to 90 days

Toxoplasma gondii

4 to 21 days

Trypanosoma cruzi

5 to 14 days

Tularemia

1 to 21 days

Typhus: endemic flea-borne, Rickettsia typhi

7 to 14 days

Typhus: epidemic louse-borne, Rickettsia prowazekii

7 to 14 days

Typhus: scrub, Rickettsia orientalis/Rickettsia tsutsugamushi

6 to 21 days

Vibrio vulnificus

1 to 4 days

Yersinia pestis

2 to 8 days

Adapted with permission from Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. Graphic 81858 Version 2.0

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Herpetic whitlow

In addition to erythema, swelling, and pain, herpetic whitlow is characterized by the presence of vesicular or pustular lesions. Patients may also experience fever, lymphadenitis, and epitrochlear or axillary lymphadenopathy. Reproduced with permission from: Nikkels AF, Peirard GE. Treatment of mucocutaneous presentations of herpes simplex virus infections. Am J Clin Dermatol 2002; 3:479. Copyright © 2002 Adis International. Graphic 75510 Version 5.0

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Cat scratch disease

This patient with cat scratch disease has a primary inoculation lesion and prominent cervical lymphadenopathy (arrow). Courtesy of Joy D Jester. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 59249 Version 3.0

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Ulceroglandular tularemia

The primary inoculation site in this patient with ulceroglandular tularemia is an ulcerated nodule that is accompanied by lymphadenopathy. Courtesy of Charles V Sanders. (The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 75954 Version 3.0

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Erysipeloid

Erysipeloid is the localized cutaneous form of the infection caused by Erysipelothrix rhusiopathiae. In this patient, violaceous maculopapular lesions of the fingers developed after cleaning fish. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 55885 Version 4.0

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Lymphocutaneous sporotrichosis

Lymphocutaneous sporotrichosis on the right lower extremity of a young man who overturned his dirt bike and inoculated soil in multiple places in his leg. Following a plastic surgery procedure before the diagnosis of sporotrichosis, new lesions developed at the edge of the skin graft and extended up into the thigh. Courtesy of Carol A. Kauffman, MD. Graphic 65985 Version 2.0

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Erythema migrans

Erythema migrans with central clearing and a necrotic center. Courtesy of Dori F Zaleznik, MD. Graphic 81270 Version 1.0

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Hot tub folliculitis

This form of folliculitis is caused by Pseudomonas aeruginosa and can occur after exposure to hot tubs or whirlpools. Courtesy of Charles V Sanders. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 65119 Version 4.0

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Primary syphilis

Primary chancre on the labia majora. Chancres are painless and frequently can be missed, especially in women. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 50385 Version 5.0

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Genital herpes

Multiple grouped vesicles of genital herpes on the shaft of the penis. These lesions are frequently painful. Courtesy of Larry Millikan. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 78603 Version 5.0

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Lymphogranuloma venereum

A dramatic case of lymphogranuloma venereum shows chronic ulcerating lymph nodes and prominent edema. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 73707 Version 3.0

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Chancroid ulcer on penis

Penile ulcer due to chancroid which is accompanied by marked inguinal lymphadenitis Graphic 76843 Version 1.0

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Donovanosis

Numerous ulcerogranulomatous, friable lesions are visible in the inguinal area and on the scrotum in a patient with donovanosis. Courtesy of Lee T Nesbitt, Jr.; The Skin and Infection: A Color Atlas and Text, Sanders, CV, Nesbitt, LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 58925 Version 3.0

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Characteristics of sexually transmitted genital ulcers Primary syphilis

Genital herpes

Chancroid

Lymphogranuloma venereum

Donovanosis

Etiology

Treponema pallidum

Herpes simplex

Haemophilus ducreyi

Chlamydia trachomatis

Calymmatobacterium granulomatis

Incubation

9 to 90 days;

2 to 7 days

Range 1 to 35

3 days to 3 weeks;

Precise data

period

average 2 to 4 weeks

days; average 3 to 7 days

average 10 to 14 days

unavailable; probably a few days to several months

Number of lesions

Usually single lesion, but multiple lesions

Multiple; may coalesce; more lesions appear in

Usually 1 to 3, but multiple lesions may

Usually single

Single or multiple

may occur

primary episodes than in

occur

recurrences Appearance of genital

Sharply demarcated

Small superficial grouped vesicles

Deep, sharply demarcated

Papule, pustule, vesicle, or ulcer;

Sharply defined irregular ulcerations

ulcers

round or oval ulcer with slightly

and/or erosions; lesions may coalesce, forming

ulcer; irregular ragged undermined

discrete and transient; frequently overlooked.

or hypertrophic, verrucous, necrotic, or cicatrical

elevated edges; may be irregular or

bullae or large areas of ulceration;

edge; ranges in diameter from a few ml

symmetrical ("kissing

lesions have irregular borders.

to 2 cm.

Bright, red, and smooth.

Rough, uneven, yellow to gray

granulomas.

chancre"). Base

Red, smooth and shiny, or crusted; serous exudate occurs when

Variable.

in color.

granulations; can be necrotic, verrucous, or

squeezed. Induration

Firm; does not change shape with pressure.

Usually friable, rough, beefy

cicatrical. None.

Soft; changes shape with

None.

Firm granulation tissue.

pressure.

Adapted with permission from Martin DH, Mroczkowski TF: Sexually Transmitted Diseases. In: The Skin and Infection: A Color Atlas and Text. Sanders CV, Nesbitt LT (Eds). Baltimore, Maryland: Williams & Wilkins, 1995, p. 95. Graphic 60432 Version 2.0

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Characteristics of sexually transmitted genital ulcers Primary syphilis Pain

Genital herpes

Painless; may

Common; more

become tender if secondarily infected.

prominent with initial infection than with

Chancroid

Lymphogranuloma venereum

Donovanosis

Common

Variable

Rare

recurrences. Inguinal lymphadenopathy

Unilateral or bilateral; firm,

Usually bilateral, firm, and tender;

Unilateral (rarely

Unilateral or bilateral; initially movable, firm,

Pseudobuboes; subcutaneous

movable, and nontender; do not suppurate.

more common in primary episodes than in recurrences.

bilateral); overlying erythema;

and tender; later indolent; fixed and matted; "sign of

perilymphatic granulamotous lesions that

matted, fixed, and

Groove" may suppurate; fistulas.

produce inguinal

tender; may suppurate. Constitutional

Rare

symptoms

Rare

Frequent

Rare

May

Local lesions heal;

Worsens

progress to erosive

systemic disease may progress;

slowly.

lesions.

disfigurement; late complications.

episode; less likely in recurrences.

Course of

Slowly resolves to

disease if untreated

latency (2 to 6 weeks).

Diagnostic tests

Common in primary

swelling.

Typically recurs.

Darkfield exam,

Tzanck smear,

Culture,

Lymphogranuloma

"Donovan

direct immunofluorescence, FTA-ABS, VDRL.

culture, Pap smear, direct immunofluorescence,

biopsy (rarely done); Gram

venereum (LGV) complement fixation test; isolation of the

bodies" in tissue smears; biopsy.

electron-microscopy, direct

stained smears have

microorganism by culture.

immunoperoxidase staining, serology.

low specificity.

Adapted with permission from Martin DH, Mroczkowski TF: Sexually Transmitted Diseases. In: The Skin and Infection: A Color Atlas and Text. Sanders CV, Nesbitt LT (Eds). Baltimore, Maryland: Williams & Wilkins, 1995, p. 95. Graphic 68988 Version 2.0

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Secondary syphilis

Maculopapular rash on the palms, which rarely can be pustular, in a patient with secondary syphilis. Patients can be quite contagious at this stage. Courtesy of David H Martin and Tomasz F Mroczkowski. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 65500 Version 6.0

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Condyloma lata

Flat condyloma lata lesions which are moist in a woman with secondary syphilis. Courtesy of David H Martin and Tomasz F Mroczkowski. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 56162 Version 6.0

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Tertiary syphilis

Noduloulcerative lesions in a ring-like distribution on the posterior thigh, known as lues maligna, in a patient with tertiary syphilis. Courtesy of David H Martin and Tomasz F Mroczkowski. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 51169 Version 5.0

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Differential diagnosis of fever and rash based upon appearance of the rash Macules, papules, nodules, or plaques

Vesicles,

Purpuric macules,

Followed widespread

bullae, or

purpuric papules, or

erythema with or without

pustules

purpuric vesicles

edema by desquamation

Bacterial Arcanobacterium

Bacillus

haemolyticum

anthracis

Bacillus anthracis

Ehrlichia canis

Bartonella bacilliformis

Listeria

Bartonella henselae (cat scratch disease) Bartonella quintana (trench fever) Borrelia burgdorferi (Lyme disease)* Borrelia spp (relapsing fever) Brucella spp (brucellosis)* Calymmatobacterium granulomatis (donovanosis)*

Bacteremia Δ Borrelia spp Clostridium spp

monocytogenes

Infective endocarditis (many species)

Mycoplasma pneumoniae

Haemophilus influenzae type B

Neisseria gonorrhoeae* Neisseria meningitidis* Pseudomonas aeruginosa Rickettsia akari Rickettsia rickettsii* Staphylococcus

Neisseria meningitidis (acute or chronic meningococcemia)* •

Pseudomonas aeruginosa Rickettsia prowazekii Rickettsia rickettsii • Spirillum minor Staphylococcus aureus

Ehrlichiosis*

Streptococcus group A

Streptobacillus moniliformis

Human granulocytic erlichiosis (HGE) Erysipelothrix rhusiopathiae (erysipeloid)

pallidum (secondary syphilis) Vibrio vulnificus

Stapylococcus aureus (toxic shock syndrome [TSS], scalded skin syndrome [SSSS])

(disseminated gonococcal infection)* •

aureus (TSS, SSSS)

Treponema

streptococcal toxic shock syndrome)

Neisseria gonorrhoeae

Chlamydia psittaci (psittacosis)

Ehrlichia chafeensis (HME)

Streptococcus group A (scarlet fever,

(bacteremia)

Streptococcus group A (streptococcal toxic shock syndrome, scarlet fever) Streptococcus pneumoniae (asplenic patient) Vibrio vulnificus Yersinia pestis

Francisella tularensis (tularemia) Listeria monocytogenes Leptospira sp (leptospirosis)* Mycobacterium leprae* Mycobacterium marinum* Mycobacterium tuberculosis Mycoplasma pneumoniae Neisseria gonorrhoeae (gonorrhea)* Neisseria meningitidis (meningococcemia)* Pseudomonas aeruginosa Rickettsia akari

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Fever and rash in the immunocompetent patient (rickettsialpox) Rickettsia prowazekii (epidemic/louse-borne typhus) Rickettsia rickettsii

(RMSF-early lesions)* • Rickettsia orientalis/tsutsugamushi (scrub typhus) Rickettsia typhi (endemic/murine typhus) Salmonella typhi (typhoid fever)* Spirillum minor (rat-bite fever) * Reportable disease. • May have arthralgia or musculoskeletal pain. Δ Specific therapy available. Adapted with permission from: Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. Originally modified with permission from Fitzpatrick TB, et al: Color Atlas & Synopsis of Clinical Dermatology - Common and Serious Diseases. Fitzgerald TB, et al (Eds), McGraw-Hill, New York, 1992. Graphic 52167 Version 6.0

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Differential diagnosis of fever and rash based upon appearance of the rash Macules, papules, nodules, or plaques

Vesicles,

Purpuric macules,

Widespread erythema with

bullae, or

purpuric papules, or

or without edema followed

pustules

purpuric vesicles

by desquamation

Fungal Blastomyces dermatitidis* Candida spp

Histoplasma capsulatum

Coccidioides immitis Cryptococcus neoformans Histoplasma capsulatum Other disseminated deep fungal infections in immunocompromised patients Viral Adenovirus Arbovirus Atypical measles* Colorado tick fever Coxsackieviruses A and B Cytomegalovirus, primary infection

Colorado tick fever

Atypical measles*

Coxsackie A5, 9, 10, 16, B2, 7

Colorado tick fever

Echoviruses

Congenital cytomegalovirus

Eczema

herpeticumΔ

Dengue virus

Herpes simplex (disseminated) Δ

Epstein-Barr virus, primary

Varicella

infection

(chickenpox) Δ

Echoviruses

Varicella-zoster

Hepatitis B (urticaria)*

Adenovirus (rare)

(disseminated) Δ

Human herpesvirus 6 (exanthem subitum)*

Kawasaki syndrome (presumed viral)

Coxsackie A and B (rare, types A-9, B2-5) Dengue fever Epstein-Barr virus (rare) Echoviruses (rare, types 3, 4, 9) Rubella* Varicella zoster virus Yellow fever

Human immunodeficiency virus (HIV-1)* Kawasaki syndrome (presumed viral) Molluscum contagiosum Orf Parvovirus B19 (erythema infectiosum [fifth disease]) Rubella (German measles)* • Rubeola (measles)* Varicella (chickenpox)* Varicella zoster (disseminated) Viral hemorrhagic fevers (many) * Reportable disease. • May have arthralgia or musculoskeletal pain.

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Δ Umbilicated papule or vesicle a characteristic of these exanthems. Adapted with permission from: Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. Originally modified with permission from Fitzpatrick TB, et al: Color Atlas & Synopsis of Clinical Dermatology - Common and Serious Diseases. Fitzgerald TB, et al (Eds), McGraw-Hill, New York, 1992. Graphic 63955 Version 4.0

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Differential diagnosis of fever and rash based upon appearance of the rash

Macules, papules,

Vesicles, bullae, or

nodules, or plaques

pustules

Purpuric macules, purpuric papules, or purpuric vesicles

Widespread erythema with or without edema followed by desquamation

Protozoal/parasitic Leishmania braziliensis

Plasmodium falciparum (blackwater fever)*

Leishmania mexicana

Trichinella spiralis

Leishmania tropica

(trichinosis)

Necator americanus

Toxoplasma gondii

Onchocerca volvulus Schistosoma Strongyloides stercoralis Toxoplasma gondii (toxoplasmosis) Trichinella spiralis (trichinosis) Trypanosoma sp Noninfectious Erythema multiforme Systemic lupus

Erythema multiforme bullosum

erythematosus

Toxic epidermal necrolysis

Dermatomyositis

Dermatitis from plants

Drug hypersensitivities

Drug hypersensitivities

Gianotti-Crosti syndrome Inflammatory bowel

"Allergic" vasculitis •

Erythroderma

Erythroderma

Drug hypersensitivities

Cholesterol embolization

Graft-versus-host reaction

Disseminated intravascular

Stevens-Johnson syndrome

coagulation (purpura fulminans) Δ

Drug hypersensitivities

disease

Fat embolism

Pityriasis rosea (fever rare)

Henoch-Schönlein purpura

Sarcoidosis

Immune thrombocytopenic purpura

"Serum sickness" •

Granulomatosis with

Sweet syndrome (acute

Toxic epidermal necrolysis von Zumbusch pustular psoriasis

polyangiitis (Wegener's)

febrile neutrophilic dermatosis) Still's disease (juvenile idiopathic arthritis) * Reportable disease. • May have arthralgia or musculoskeletal pain. ​ Δ Often present as infarcts. Adapted with permission from: Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. Originally modified with permission from: Fitzpatrick TB, et al: Color Atlas & Synopsis of Clinical Dermatology - Common and Serious Diseases. Fitzgerald TB, et al (Eds), McGraw-Hill, New York, 1992. Graphic 71663 Version 8.0

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Differential diagnosis of fever and rash based upon accompanying signs Arthritis or arthralgia

Desquamation

Acute meningococcemia

Arcanobacterium

Allergic purpura Disseminated gonococcal infection Erythema marginatum (acute rheumatic fever) Hepatitis B virus, prodromal phase

haemolyticum infection Drug hypersensitivity Graft-versus-host reaction Kawasaki syndrome Measles

Lyme disease

Rocky Mountain spotted fever

Parvovirus B19

Scarlet fever

Reiter's syndrome Rocky Mountain spotted fever Roseola (especially in adults) Rubella Serum sickness

Staphylococcal scaldedskin syndrome Stevens-Johnson syndrome Toxic epidermal necrolysis

Still's disease

Toxic shock syndrome

Systemic lupus

von Zumbusch pustular psoriasis

erythematosus

Lymphadenopathy Cervical

Meningitis Acute meningococcemia

Kawasaki syndrome

Cryptococcosis

Rubella

Enterovirus

Scarlet fever Generalized Infectious mononucleosis Secondary syphilis Serum sickness

(Coxsackieviruses, echoviruses) Leptospirosis Lyme disease Rocky Mountain spotted fever Secondary syphilis

Sarcoidosis Systemic lupus erythematosus Toxoplasmosis Hilar Atypical measles Sarcoidosis Local Cat-scratch disease Tularemia

Adapted with permission from Adapted with permission from Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. With permission from Hurst JW (Ed). Medicine for the Practicing Physician., 3rd ed, Butterworth-Heinemann, Boston, 1992, p. 273. Graphic 78412 Version 2.0

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Differential diagnosis of fever and rash based upon accompanying signs Mucosal membrane lesions (enanthems)

Palm-sole involvement

Pulmonary infiltrate

Herpes simplex

Acute meningococcemia

Atypical measles

Infectious mononucleosis (palatal

Atypical measles

Coccidioidomycosis

Dengue

Cryptococcosis

Drug rash

Fat embolism

Erythema multiforme

Histoplasmosis

Hand-foot-mouth disease

Mycoplasma pneumoniae

Kawasaki syndrome

North American blastomycosis

petechiae) Measles (Koplick's spots) Strawberry tongue Atypical measles Kawasaki disease Scarlet fever Toxic shock syndrome

Varicella zoster

Ulcerative or vesicular stomatitis Hand-foot-mouth disease Herpes simplex Histoplasmosis Inflammatory bowel disease Secondary syphilis Systemic lupus erythematosus

Measles Rocky Mountain spotted fever Secondary syphilis Staphylococcus aureus endocarditis

Rash predominantly on extremities

Psittacosis Rocky Mountain spotted fever Sarcoidosis Varicella zoster

Allergic purpura Brucellosis Disseminated gonococcal infection Ecthyma gangrenosum Erythema nodosum Sporotrichosis (fever rare)

Adapted with permission from Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. With permission from Hurst JW (Ed). Medicine for the Practicing Physician, 3rd ed, Butterworth-Heinemann, Boston, 1992, p. 273. Graphic 54445 Version 2.0

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Erythema multiforme

Characteristic target lesions of the palm in erythema multiforme begin with a central vesicle. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995.

http://www.lww.com Graphic 74095 Version 5.0

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Causes of erythema multiforme Contact reactions Tadania ignis (fire sponge)

Drugs Allopurinol Antituberculous agents Barbiturates Carbamazepine Oral hypoglycemic agents NSAIDs Phenytoin Sulfonamides

Endocrine factors Pregnancy

Idiopathic >50 percent

Infections Epstein-Barr virus Francisella tularensis Hemolytic streptococci Herpes simplex 1 and 2 Histoplasma capsulatum Mycoplasma pneumoniae Mycobacterium tuberculosis Proteus sp Salmonella sp Staphylococcus sp Vibrio parahaemolyticus Yersinia sp

Physical Sunlight X-ray therapy Adapted with permission from Sanders CV, Diagnosis of the Patient with Fever and Rash. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. Originally modified with permission from Dermatology in General Medicine, Fitzpatrick TB, et al (Eds), McGraw-Hill, New York, 1993. Graphic 72248 Version 2.0

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Erythema nodosum

Painful erythematous nodules of erythema nodosum are often found in a symmetric distribution on the legs. The nodules can also appear to be pigmented. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore. 1995.

http://www.lww.com Graphic 80056 Version 5.0

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Toxic epidermal necrolysis

Usually caused by drugs, toxic epidermal necrolysis demonstrates widespread erythema and confluent vesiculation, leading to sloughing of the skin. Affected patients are at risk for hypernatremic dehydration and sepsis. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 66134 Version 5.0

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Causes of toxic epidermal necrolysis Drugs

Infections

Alka-Seltzer®

Aspergillosis (pulmonary)

Allopurinol*

Escherichia coli (septicemia)

Amiodarone

Herpes simplex virus

Antibiotics, esp. tetracyclines and penicillin*

Measles virus

Anticonvulsants*

Varicella zoster virus

Antipyrine

Miscellaneous

Barbiturates*

Graft-versus-host disease

Brompheniramine Chlorpromazine Dapsone Ethambutol Fansidar Fenoprofen Gold Griseofulvin Ipecac Isoniazid NSAIDs Pentamidine

Idiopathic

Neoplasia Hodgkin's disease Leukemia Non-Hodgkin's lymphoma

Vaccinations BCG Diphtheria toxoid Measles Poliomyelitis Tetanus antitoxin

Phenolphthalein Quinine Streptomycin Sulfonamides* Tolbutamide Trimethoprim * Most commonly associated with toxic epidermal necrolysis (TEN). Adapted with permission from Sanders CV. Diagnosis of the patient with fever and rash. In: The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT (Eds), Williams & Wilkins, Baltimore, 1995. With permission from Rohrer TE, Ahmed AR. Toxic epidermal necrolysis. Int J Dermatol 1991; 30:457. Graphic 65062 Version 3.0

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Giant urticaria

Very large erythematous annular lesion of the shoulder with central clearing. This patient had several large lesions of this type which could be confused with erythema migrans. Courtesy of Lee T Nesbitt, Jr. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 81678 Version 3.0

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Infectious agents and illnesses associated with urticaria Agent

Illness

Bedbugs, kissing bugs, ants, fleas, flies, and mosquitoes

Bites and stings

Coxiella burnetii

Q Fever

Coxsackieviruses A9, A16, B4, B5

Rash

Echinococcus sp

Echinococcosis

Echovirus 11

Rash

Epstein-Barr virus

Infectious mononucleosis

Entamoeba histolytica

Amebiasis

Enterobius vermicularis

Pinworm infestation

Giardia lambdia

Giardiasis

Hepatitis B virus

Hepatitis B

Mites

Bites

Mumps virus

Mumps

Mycoplasma pneumoniae

Atypical pneumonia

Necator americanus

Hookworm disease

Neisseria meningitidis

Meningococcemia

Plasmodium sp

Malaria

Pediculus humanus

Pediculosis

Sarcoptes scabiei

Scabies

Schistosoma sp

Schistosomiasis

Shigella sonnei

Shigellosis

Trichinella spiralis

Trichinosis

Trichobilharzia sp

Swimmer's itch; collector's itch

Trichomonas vaginalis

Vulvovaginitis

Trombicula irritans

Chigger bites

Wuchereria bancrofti

Filariasis

Yersinia enterocolitica

Yersiniosis

Adapted with permissiom from Sanders CV, Diagnosis of the Patient with Fever and Rash. In: The Skin and Infection: A Color Atlas and Text. Sanders CV, Nesbitt LT (Eds), Baltimore, Maryland: Williams & Wilkins, 1995. Originally modified from Textbook of Pediatric Infectious Diseases, 3rd ed, Vol 1, Feigin RD and Cherry JD (Eds), Philadelphia, WB Saunders, Philadelphia 1992, p. 771. Graphic 74764 Version 2.0

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Purpura fulminans

Skin lesions in acute meningococcemia can begin as papules but quickly progress to petechiae and purpura. As seen here, the purpuric lesions can coalesce. Courtesy of Charles V Sanders. (The Skin and Infection: A Color Atlas and Text, Sanders, CV, Nesbitt, LT Jr (Eds), Williams & Wilkins, Baltimore, 1995). Graphic 52107 Version 2.0

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Subconjunctival petechiae in infective endocarditis

Subconjunctival petechiae are prominent in this case of bacterial endocarditis caused by Staphylococcus aureus. Courtesy of Jan V Hirschmann. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 59982 Version 6.0

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Splinter hemorrhages in infective endocarditis

Splinter hemorrhages, linear reddish-brown lesions, are seen in the nail bed of this patient with bacterial endocarditis due to group B Streptococcus. Courtesy of Gene Beyt. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995.

http://www.lww.com Graphic 72076 Version 9.0

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Janeway lesion in infective endocarditis

A Janeway lesion (arrow) occurred on the palm in this patient with bacterial endocarditis due to Streptococcus bovis. These lesions are macular, nonpainful, and erythematous; they are located on the palms and soles. Courtesy of Jan V Hirschmann. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995.

http://www.lww.com Graphic 58380 Version 15.0

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Osler's nodes in infective endocarditis

Osler's nodes are tender papulopustules located on the pulp of the finger in a patient with bacterial endocarditis caused by Staphylococcus aureus. Courtesy of Charles V Sanders. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore 1995.

http://www.lww.com Graphic 68796 Version 8.0

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Rocky mountain spotted fever

Extensive maculopapular and petechial lesions on the trunk and thigh in a patient with Rocky Mountain spotted fever. The rash characteristically begins on the wrists and ankles and spreads centripetally. Courtesy of Harold G Muchmore. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams &Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 67850 Version 5.0

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Rash in Staphylococcal toxic shock syndrome

Erythematous maculopapular eruption on the abdomen in a patient with staphylococcal toxic shock syndrome (TSS). The erythroderm of TSS can be subtle and resemble a sunburn. Courtesy of Charles V Sanders. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 77600 Version 4.0

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Conjunctival suffusion in Staphylococcal toxic shock syndrome

Conjunctival suffusion in a patient with staphylococcal toxic shock syndrome (TSS). Courtesy of Charles V Sanders. The Skin and Infection: A Color Atlas and Text, Sanders CV, Nesbitt LT Jr (Eds), Williams & Wilkins, Baltimore, 1995.

http://www.lww.com Graphic 66457 Version 4.0

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