Selected Dermatologic Emergencies: Recognition, Differential Diagnosis, and Init
July 5, 1998
Selected Dermatologic Emergencies: Recognition, Differential Diagnosis, and Initial Therapeutic Considerations for the Emergency Physician
Part II: Infectious Disease Syndromes with Dermatologic Presentations
Author: William J. Brady, MD, FACEP, Assistant Professor of Emergency Medicine and Internal Medicine, Department of Emergency Medicine, University of Virginia School of Medicine, Charlottesville, VA; Medical Director, Chest Pain Center, Department of Emergency Medicine, University of Virginia Health System, Charlottesville, VA.
Peer Reviewer: David A. Kramer, MD, FACP, Associate Professor of Emergency Medicine, Emergency Medicine Residency Program Director, Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA.
In this second part of a two-part series, the author provides detailed clinical strategies for diagnosis and management of common, and, in some cases, life-threatening diseases that present with prominent dermatological manifestations. Beginning with herpes zoster infection and culminating with syndromes characterized by widespread blistering, this review is accompanied by a visual legend that will identify these conditions at the front lines of emergency care.
-The Editor
Herpes Zoster Infection
Both acute varicella and varicella zoster infections are caused by the same virus-Herpesvirus varicellae. The primary infection is acute varicella, which manifests in childhood as chicken pox. In contrast, varicella zoster infections (VZI) represent reactivation of a previously dormant virus in a patient with incomplete or compromised immunity; VZI is also referred to as shingles. In the case of the initial illness (i.e., chicken pox), the virus travels via individual cutaneous nerves to the dorsal root ganglia, where it remains latent until reactivation. At the time of reactivation, which usually occurs as a result of diminished immunologic function, the virus migrates down specific sensory nerves to the skin and produces shingles.
The specific factors leading to VZI are unknown, but likely involve reduced immune function in patients with a significant comorbid illness and/or medications associated with immunosuppressive properties. In particular, patients with lymphoma, leukemia, and diabetes mellitus are at highest risk for development of VZI. In addition, patients with altered immune function due to medication effects, organ transplant recipients, and patients with severe rheumatologic illness are more likely to acquire VZI. In most cases, it is difficult to determine whether the primary illness or medical therapy is responsible for reactivation.
Patients of all ages can be afflicted with VZI, with 10% of the population experiencing at least one episode of VZI in their lifetime.1 However, children who develop chicken pox before the first 2 months of age are reported to be at increased risk for VZI later in life.2 In addition, patients with an "unexplained" episode of VZI should be questioned about risk behaviors for HIV infection; appropriate testing should follow inasmuch as VZI may be an early manifestation of the acquired immunodeficiency syndrome in high-risk individuals.3 Generally speaking, an exhaustive search for an underlying malignancy is probably not warranted in patients with VZI, since patients with VZIs are not more likely to have cancer.4
Patients with no documented history of chicken pox also may present with VZI. These cases result from either transplacental exposure to varicella or they have had a mild case of chicken pox that was clinically unrecognized. Contact with a patient with active shingles is unlikely to cause VZI in a patient with past chicken pox; however, the patient without a previous episode of varicella infection can acquire chicken pox from such an exposure.
Clinical Presentation and Diagnosis. The rash associated with shingles is characterized by vesicles and/or papules grouped together on an erythematous base. Classical features of this herpes infection include the close grouping or clustering of lesions arrayed in an inflamed area of otherwise normal skin. (See Table 1 and Figure 1a.) The lesions initially appear as papulovesicles with clear fluid; over several days, the fluid within the vesicles may become cloudy and may eventually rupture. Eventually, there is blister and ulcer formation. The lesions vary in size in contrast to the vesicles seen in the Herpes simplex infections. (See Figure 1a.)
As a rule, the lesions of VZI appear along an individual dermatome. (See Figures 1b and 1c.) Occasionally, adjacent dermatomes may be involved. About two-thirds of all zoster infections involve the trunk, followed by the head and facial region, extremities, and perineal regions. In the case of VZI involving the truncal area, lesions may appear over a period of several days in centripetal fashion, with the initial cluster often located on the patient's back, just lateral to the midline. (See Figure 1b.) Subsequent lesions "move around the dermatome" toward the patient's flank and eventually around to the anterior aspect of the thorax over a 5-10 day period. As a rule, the clusters are discrete and are separated by areas of normal skin (See Figure 1b); in severe cases, the cluster may become confluent along the dermatome.
Unilateral involvement, which abruptly halts at the midline, is helpful in identifying the rash of VZI; occasionally, a few lesions may erupt just beyond the midline, and this is not inconsistent with the diagnosis. Approximately 50% of cases with VZI, especially patients with AIDS or reticuloendothelial malignancy, will experience viremia. These individuals may exhibit solitary lesions, usually totaling less than 30, which are scattered across the body. This finding, alone, does not indicate disseminatiof the disease. Patients with AIDS, individuals on immunosuppressive medications, and those with active reticuloendothelial malignancy more often demonstrate dissemination. Patients with Hodgkin's disease are especially prone to dissemination, with 15-50% of cases demonstrating involvement of the skin, lungs, and central nervous system. This group has a 10-25% mortality.5 Death from VZI is rare in patients with other types of malignancy.
Pain, which may precede the skin manifestations by 4-5 days, is a prominent symptom in most patents, especially in the elderly.6 Interestingly, intense pain is a less often encountered complaint in the young patient.6 Complaints of pain prior to the presence of skin lesions may make the diagnosis difficult, especially in the older patient. A high index of suspicion is required during the initial prodrome, and the diagnosis should be considered in individuals who report severe head, chest, back, or abdominal pain occurring in a dermatomal distribution.
Other sensations that may be noted include pruritus, paresthesias, hypesthesia, and hyperesthesia. Constitutional symptoms such as fever, myalgias, and headache may also be reported by patients at the onset of illness. These prodromal symptoms, including the segmental pain, usually decrease in severity or resolve with appearance of the skin lesions. As is the case with pre-eruptive dermatomal pain, younger patients are less likely to experience other prodromal symptoms. The emergency physician must also be aware of and direct attention toward the psychosocial issues of the the patient with VZI; many older patients will note a sense of helplessness and depression during this infection.6 In fact, suicide, with the VZI as the triggering event, has been reported.
Ocular involvement, which is common in patients with VZI, affects the ophthalmic branch of the fifth cranial nerve (See Figure 1d.) Corneal involvement is likely if vesicular lesions are observed in the lateral portion of the nose, implicating the nasociliary nerve. (See Figure 1d.) Hutchinson's sign is noted with lesions involving the distal portion of the nose. This degree of involvement may range from a keratoconjunctivitis without sequelae to a severe keratitis with vision-threatening corneal ulceration and scarring.
Table 1. Lesions of Varicella Zoster (Shingles)
· Close grouping/clustering of lesions
· Arrayed on an erythematous base
· Papulovesicles with clear/purulent fluid
· Ultimate ulcer formation with crusting
· Lesions vary in size
Fluorescein staining in conjunction with a comprehensive slit lamp examination of the cornea is essential in all cases of facial VZI. It should be stressed that a negative examination in a patient who has an obvious vesicular rash in the distribution of the third ophthalmic branch of the trigeminal nerve should not dissuade the EP from considering the possibility of corneal involvement; pain and skin lesions frequently appear before any objective ophthalmological findings are observed. The presence of Hutchinson's sign should alert the EP to the possibility of eventual corneal involvement-whether or not corneal lesions are noted at the time of initial examination. In contrast to ophthalmologic findings, involvement of the maxillary and mandibular branches of the fifth nerve will produce intraoral vesicles.
In addition to sensory complaints, other neurologic findings include paralysis and bladder dysfunction. Motor impairment is not common, although partial paresis of an extremity may be seen; complete return of motor function can be expected. The Ramsey Hunt syndrome is seen in patients with facial VZI. Viral movement along the seventh cranial nerve from the geniculate ganglion produces pain in the auricular and lateral facial areas. In addition, vesicles are seen on the tympanic membrane, in the external auditory canal, and on the concha and pinna. Facial nerve paralysis and hearing deficits are common. Auditory nerve involvement is seen in approximately 40% of cases, and is accompanied by partial hearing loss and vertigo.7 Sacral VZI may produce bladder dysfunction with S2, S3, and/or S4 dermatomal involvement. Regional lymphadenopathy may also be seen in these patients.
Mild cases of VZI will heal uneventfully in 2-4 weeks, whereas severe infections will produce more extensive skin surface involvement, with ulceration and secondary staphylococcal infection. The following factors are associated with an increased risk for severe, localized VZI: older age, HIV infection, ongoing immunosuppressive therapy, and reticuloendothelial malignancy. Scarring, hypopigmentation, and keloid formation are not uncommon. VZI in the pregnant patient, regardless of stage of pregnancy, does not appear to affect either the mother or the fetus.
Postherpetic neuralgia. Postherpetic neuralgia may be the most dreaded complication of the disease. This type of pain is the major cause of morbidity in patients with recent or remote zoster infections; the mechanism for postherpectic neuralgia been established. From a clinical perspective, however, the pain is often severe, intractable, and exhausting; elderly patients have committed suicide due to the severe pain and lack of relief. The incidence of pain increases with age as does both the magnitude and the duration of pain. The majority of patients under age 30 years do not experience postherpetic pain. By age 40, however, the risk of prolonged pain increases to approximately 30% and, by age 70 years, to 75%.6 Interestingly, the severity of subsequent pain is not related to the lesion size or severity of the initial infection.8 Patients with VZI involving the fifth cranial nerve reportedly experience postherpetic pain more often and for longer periods than do individuals with other VZI in other dermatomal distributions.
The differential diagnosis of herpes zoster infection is broad. (See Table 2.) Any process involving focal blistering and necrosis can produce similar lesions. Accordingly, the differential diagnosis of herpes zoster infection includes dermatitis herpetiformis, H. simplex virus infection, contact dermatitis (e.g., eczematous dermatitis), primary blistering disorders (pemphigus vulgaris and bullous pemphigoid), fixed drug eruptions, erythema multiforme, pyoderma gangrenosum, focal vasculitis, purpura fulminans, diabetic ulcer, bedsores, thermal/friction blisters, and factitious injection. Neuralgia occurring in an erythematous area and lacking vesicular lesions may also be confused with bacterial cellulitis.
Table 2. Differential Diagnosis of Varicella Zoster (Shingles)
· Dermatitis herpetiformis
· Herpes simplex virus infection
· Contact dermatitis (e.g., eczematous dermatitis)
· Primary blistering disorders (pemphigus vulgaris and bullous pemphigoid)
· Fixed drug eruptions
· Erythema multiforme
· Pyoderma gangrenosum
· Focal vasculitis
· Purpura fulminans
· Diabetic ulcer
· Bedsores
· Thermal/friction blisters
· Factitious injection
· Bacterial cellulitis
Management. Most cases of VZI should be treated with reassurance, oral and/or parenteral pain medication as required, antihistamines, and topical therapy. Many patients are concerned about the disfiguring nature of the lesions; the physician should provide reassurance that lesions will resolve without such sequelae. As a rule, pain should be managed with oral NSAIDs and/or narcotic agents; parenteral narcotic agents may be helpful in patients with severe pain, which may require multiple administrations; alternatively, pain of less than five weeks duration may be treated with regional nerve block or epidural anesthesia. Antihistamine therapy may help relieve the intense pruritic and/or burning sensations encountered in the elderly patient.
Cool compress (tap water or Burow's solution) and calamine lotion will provide relief for superficial pain and pruritus. Such compresses applied for 15-20 minutes four times daily will macerate vesicles, remove crusts, and suppress bacterial growth. Short periods in a cool shower will also reduce superficial skin complaints. Topical steroids are not of benefit. Patients should also be cautioned about contagion toward contacts without a prior history of varicella infection.
Intravenous and oral high-dose acyclovir, if instituted within 48-72 hours of lesion appearance, may reduce discomfort, duration, and the intensity of the infection. There is also evidence to suggest that acyclovir and valacyclovir will reduce the likelihood of developing postherpetic neuralgia.9,10 In general, acyclovir should be offered to patients who present early in the disease course (i.e., within 72 hours of eruption). Antiviral therapy is strongly recommended in patients who have large lesions, in those who have significant comorbidity, in patients who are using immunosuppressive medications, or those who have ophthalmic zoster. After 72 hours of symptoms, such therapy is unlikely to be of much benefit in the immunocompetent patient.11,12 Approximately 50% of patients with VZI will present to the physician within this three-day time period, and therefore, will be candidates for this therapeutic approach.6
It should be stressed that other antiviral agents are available for the acute treatment of VZI. In addition to acyclovir, valacyclovir 44c and famciclovir 44d also are acceptable.13 In general, these agents do not offer significant advantage over acyclovir in the treatment of VZI except for reduced dosing frequency, which may increase compliance and, therefore, improve outcome.
Patients and physicians should recognize the importance of initiating antiviral therapy as soon as symptoms are noted and the diagnosis can be confirmed. In this regard, administration of the initial dose of the antiviral agent in the emergency department (ED) represents a sound approach, since reduction of symptoms and minimizing post-herpetic neuralgia are both time-sensitive phenomena. In addition to temporal barriers to the success of antiviral therapy, cost factors also must be considered. Antiherpetic agents are costly. In this regard, a recent survey of patients with VZI demonstrated that the majority were unwilling to use expensive agents if success was not likely.6 (See Table 3 for a listing of the various antiviral agents available for treatment of the VZI patient.)
The use of systemic steroids for reducing the incidence of postherpetic neuralgia is controversial. As a rule, it is prudent to discuss this option with a dermatologist or an infectious disease consultant on an individual, case-by-case basis. Several reports suggest that if systemic steroids are used early in the eruptive stage of the illness, they may reduce the likelihood of postherpetic pain. Clearly, however, the use of steroids late in the disease course does not produce benefit. In any event, the risk of precipitant disseminated disease is minimal in patients who do not have a malignancy or immunodeficiency disorder.
Patients with severe VZI may require inpatient therapy and urgent dermatologic consultation, but this is the exception rather than the rule. Such cases are characterized by pain unresponsive to oral agents; large areas of local infection requiring aggressive wound care; secondary bacterial infection of herpetic skin lesions; active immunosuppressive or antineoplastic medication therapy; ophthalmic zoster; focal neurologic deficits; or disseminated disease.
Table 3. Oral Antiviral Therapy Used in the Management of VZI
MEDICATIODOSE
Zivorax (acyclovir) |
800 mg po 5 times/24 hr |
Valtrex (valacyclovir) |
1 g po q8h for 7 days |
Famvir (famciclovir) |
500 mg po q8h for 7 days |
Rocky Mountain Spotted Fever
Rocky Mountain spotted fever (RMSF) is a potentially fatal multisystem illness caused by Rickettsia rickettsii that is most often introduced to humans via a tick vector. RMSF has been reported in most regions of the United States, with the exception of Maine, Alaska, and Hawaii.14 The disease is most frequently encountered in the mid- and south-Atlantic coastal states. RMSF is seasonal, with the majority (95%) of cases occurring in the spring and summer. Five to 700 cases are reportedly annually in the United States. Moreover, the condition is associated with a mortality rate ranging from 3% to 7%, but only in patients who are correctly diagnosed and appropriately treated. In heavily pigmented patients, a much higher mortality rate (16%) is noted, which may reflect difficulty in detecting the characteristic rash, and subsequent delays in initiating therapy. It should be stressed that in the absence of timely management, the mortality rate increases to 30-70%.15,16
Rickettsia rickettsii is spread to humans via a tick bite. Although not proven, authorities state that the tick must remain attached to the patient for at least six hours in order to transmit disease. After introduction of the organism into body tissues, it disseminates via the blood stream, invades vascular endothelium, and multiplies, a pathophysiological sequence that accounts for the widespread, multisystem nature of the illness. The histopathology is consistent with a necrotizing vasculitis.
Clinical presentation and diagnosis. After exposure to the tick and introduction of the organism into the body, the patient usually will present with the triad of fever (94%), headache (88%), and myalgias (85%). These symptoms become prominent approximately one week (range, 3-21 days) after the tick bite. Additional complaints may include photophobia, nausea, vomiting, abdominal pain, dry cough, malaise, and confusion. Typically, the rash in classic RMSF is evident four days (range, 1-15 days) after the onset of fever and other symptoms.15 In a minority of patients (usually adults), the rash is not noted at any point of the disease course. This entity, also called Rocky Mountain "spotless" fever, occurs in approximately 15% of cases. In many instances, Rocky Mountain spotless fever may actually be Ehrliciosis.
The rash first appears on the wrists and ankles, and spreads rapidly to the palms and soles. (See Figure 2.) As the rash moves centrally, the proximal extremities, trunk, and face are involved. The skin lesions at onset are described as discrete macules or maculopapules that blanch with pressure from the examiner's finger. The initial lesions evolve into petechiae during a 2-4 day period, fade slowly over 2-3 weeks, and heal, occasionally with resultant hyperpigmentation. Rarely, the petechiae may coalesce into ecchymotic areas with eventual gangrene of the distal extremities, nose, ear lobes, scrotum, and vulva.
The overall severity of the rickettsial infection is proportional to both the magnitude of the rash and the rapidity of its progression. Additional clinical findings include focal pulmonary infiltrates; myocarditis, which can be associated with dysrhythmias and cardiogenic shock; peripheral edema caused by herpatic dysfunction and hypoalbuminemia; prerenal renal failure; various neurological findings, including altered mental status, coma, seizures, focal deficits, and meningismus with cerebral spinal fluid pleocytosis; and disseminated intravascular coagulation. The most common cause of death is irreversible, distributive shock related to visceral and central nervous system dissemination of the rickettsial organism.
Diagnosis is largely clinical, and is based on the triad of headache, fever, and myalgias in a patient who has the potential for tick exposure. Even if there is no rash at presentation, the informed clinician should not rule out the possibility of RMSF, since the dermatological manifestations develop late in the disease course, and a minority of patients have the "spotless" variety. Laboratory values are not helpful in making the initial diagnosis, but increases in antibody titer can confirm RMSF in 10 days to two weeks. Immunofluorescent staining of a skin lesion is a new technique, providing a rapid means for diagnosis that is both highly sensitive and specific. The results, however, can be difficult to interpret in inexperienced hands.
The differential diagnosis includes meningococcemia (less orderly, more rapid rash progression) and endemic typhus (dissimilar rash distribution in a less ill patient). Additional entities deserving consideration include disseminated gonococcemia, secondary syphilis, viral exanthem, and disseminated intravascular coagulation.
Management. As in other entities, attention should be paid to establishing an adequate airway with ventilation and oxygenation, coupled with insuring systemic perfusion. Antibiotic therapy includes tetracycline for nonpregnant patients older than 8 years; children and the pregnant patient are best managed with chloramphenicol. Monitoring and supportive management are best performed in a critical care setting, especially in the case of patients who present with obvious disease and the potential for multiorgan failure. Patients who present with possible RMSF (i.e., they have had possible tick exposure and symptomatology characteristic of "viral syndrome") are best managed with a course of oral antibiotic therapy and close medical follow-up.
If the patient presents with a tick embedded in the skin, it should be removed. Using blunt curved forceps, the examiner grasps the tick as close to the skin surface as possible and pulls upward with a steady even pressure. Twisting and jerking movements of the forceps may cause the tick mouth parts to remain embedded in the skin. Steady even pressure for approximately 3-5 minutes will cause the tick to slowly back out of the skin. After the tick has been removed, the wound is thoroughly cleaned and irrigated and then properly bandaged. Tetanus prophylaxis is considered at this point. During the procedure, the examiner should use rubber gloves to shield himself or herself from potential infectious disease.
An alternative method for field use involves a thread or string. A loop is made in the thread and placed over the tick closest to the skin surface. With similar gentle traction the tick is slowly removed from the skin. Regardless of the method of removal, squeezing or pressure on the tick body should be avoided since this may cause injection of tick body fluids into the patient and increase the likelihood of infection.
Meningococcal Disease
Meningococcemia is a potentially fatal infectious illness caused by the gram-negative diplococcal bacterium Neisseria meningitidis. Meningococcal disease presents across a wide clinical spectrum in both acute and chronic forms. The acute entities include pharyngitis, meningitis, sepsis, or a combination of central nervous system and systemic infection; this clinical syndrome is most frequently encountered. The chronic variant (which will not be discussed here) is rare and occurs most often in patients with specific complement deficiencies. The chronic state infrequently progresses to acute disease. Meningococci are present in the nasopharynx of 2-20% of the general population (the carrier state); during epidemics, the organism is found in up to 30% of people without evidence of active disease.17
Meningococcal disease is commonly encountered in the pediatric setting. The illness usually strikes patients younger than 20 years, with the vast majority of cases occurring in children and infants younger than 5 years. Epidemic outbreaks occur when a virulent strain of the organism is introduced into a closed, confined population. The highest rates of infection are reported in the winter and spring months, although sporadic cases appear throughout the year.18
The organism is transmitted via aerosolized droplets of respiratory secretions from asymptomatic carriers and less frequently from actively infected patients. The mortality rate ranges from 5% to 28%; the majority of patients who are treated appropriately early in the course of the disease will recover.17,19-22 It should be stressed that patients with acute meningococcal infection who exhibit signs of circulatory insufficiency, a peripheral white blood cell count of less than 10,000 cells/mm3, or a coagulopathy have a high probability of developing organ system failure followed by death.23
Clinical presentation and diagnosis. Following exposure to the organism, clinical infection usually develops within 3-4 days (range, 2-10 days) and then progresses rapidly to severe illness. The patient may complain of severe headache, sudden fever, nausea, vomiting, myalgias, arthralgia, and a stiff neck. A rash is frequently noted on presentation and is an invaluable clue to suspecting the diagnosis early in the disease course. The mental status is often altered, ranging from agitated confusion to coma. On rare occasions, the patient with fulminant disease will present in septic shock.
Dermatological manifestations of multisystem meningococcal disease include petechia, urticaria, hemorrhagic vesicles, macules, and/or maculopapules. (See Figure 3.) The classical petechial lesions are found on the extremities and trunk, but also are noted on the palms, soles, head, and mucous membranes. The petechiae evolve into palpable purpura with gray necrotic centers, which is a pathognomic finding for meningococcal infection. Skin findings result from invasion by the organism into the skin and subsequent destruction of the vascular endothelium. Histopathological analysis demonstrates an infectious vasculitis.
Fulminant meningococcal disease, which is encountered in less than 5% of patients, presents with sudden onset of prostration, petechiae with areas of ecchymosis, and distributive shock. (See Figure 3.) This rapidly progressive variant of meningococcemia is complicated by purpura fulminans, which represents an aggressive form of disseminated intravascular coagulation. Large ecchymotic areas-usually, on the extremities, acral portions of the face, and genitalia-become necrotic or gangrenous. Patients who survive this fulminant disease will have gangrenous tissue that will auto-amputate or require surgical removal.
The diagnosis of acute meningococcal disease is suggested by the presence of an ill-appearing patient with an associated petechial rash accompanied by nonspecific symptoms of fever, headache, altered sensorium, and body aches. Additional historical points, physical signs, and laboratory findings supportive of the diagnosis include known exposure to active disease, rapid progression of nonspecific symptoms with the associated petechial rash, gram stain of skin lesions or cerebral spinal fluid demonstrating gram-negative intracellular diplococci, and latex agglutination of the cerebrospinal fluid. The differential diagnosis includes RMSF, TSS, acute gonococcemia, bacterial endocarditis, vasculitis (Henoch-Schonlein prupura or leukocytoclastic vasculitis), enteroviral infections, and bacterial sepsis (gram positive and gram negative) with disseminated intravascular coagulation.
Table 4. Kawasaki Disease Diagnostic Criteria
Presence of prolonged fever (greater than 5 days) with four of the following features:
· Bilateral conjunctivitis
· Mucous membrane changes (red or fissured labia, erythematous pharynx, "strawberry" tongue)
· Polymorphous, erythematous rash (papules, vesicles, bullae, urticarial plaques)
· Extremity changes (erythema/edema of palms/soles, desquamation)
· Lymphadenopathy (at least one node measuring 1.5 cm in diameter)
Management. After stabilizing respiratory and hemodynamic parameters, parenteral antibiotics should be administered immediately. Prudent and proactive management suggests antibiotics should be administered as soon as possible in any patient suspected of acute disease. In this regard, an uncertain diagnosis or diagnostic studies such as head computerized tomographic scan should not delay empiric antibiotic administration.
Initial empiric therapy should also provide coverage of Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. Appropriate agents include third generation cephalosporins such as ceftriaxone; due to the increased prevalence of cephalosporin-resistant pneumococcus, parenteral vancomycin should also be administered on an empirical basis. Once laboratory evidence confirms meningococci, intravenous penicillin should be used; it represents the drug of choice for this infection. Chloramphenicol is an alternative agent. Chemoprophylaxis with rifampin or ciprofloxacin is used for close contacts of the patient and in medical personnel, including prehospital caregivers, who have or may have been exposed to respiratory secretions.
Kawasaki Syndrome
Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute febrile illness that occurs primarily in children; the onset occurs from the neonatal period to early adolescence and the mean age at diagnosis is 2.6 years. Rare adult cases have been reported. The diagnosis of adult KD remains a challenge due to the age presentation.24
KD was first described in Japan, although cases are commonly encountered both endemically and epidemically in the Americas, Europe, and Asia. The major clinical features include: prolonged fever with a duration greater than five days; conjunctivitis and other mucosal changes; lymphadenopathy; and erythematous exanthem, with subsequent desquamation. The precise cause of KD is not known, but an immune response to an infectious agent or environmental toxin is suspected. Both short- and long-term morbidity and mortality result from cardiac involvement in the form of myocardial infarction, malignant arrhythmias, and acute congestive heart failure. Mortality in the United States and Japan, which usually results from cardiac dysfunction, has been reported to be 1-2%.25
Table 5. Differential Diagnosis of Kawasaki Syndrome
· Erythema multiforme
· Urticarial vasculitis
· Kawasaki disease
· Toxic-infectious erythemas
· Exfoliative drug reactions
Clinical presentation and diagnosis. As with many disease states encountered in emergency medicine, the diagnosis does not depend upon a specific laboratory test. Rather, the diagnosis should be considered in a young child with unexplained, prolonged fever associated with rash and conjunctivitis. The Centers for Disease Control and Prevention in Atlanta have defined KD according to the following criteria (see Table 4): The presence of prolonged fever (greater than 5 days) accompanied by four of the following features 1) bilateral conjunctival injection (see Figure 4a); 2) mucous membrane changes (red or fissured labia, erythematous pharynx, "strawberry" tongue) (see Figures 4a and 4b); 3) erythematous rash (see Figure 4b); 4) extremity changes (erythema and edema of palms and/or soles, desquamation) (see Figure 4c); and 5) lymphadenopathy (at least one node measuring 1.5 cm in diameter). The fever is a constant feature and is usually lacking chills and sweats; it abruptly appears, spiking to 101°F to 104°F, and responds poorly to antipyretic therapy. The mean duration of fever at diagnosis is approximately nine days, with a range of five days to one month.
Mucosal changes in KD are seen in the conjunctivae as well as other areas. Conjunctivitis is an almost constant feature, and is characterized by bilateral involvement. (See Figures 4a & 4b.) Typically, the bulbar conjunctiva demonstrates congestion; at times, the palpebral portion of the conjunctiva is also affected. Uveitis is frequent, and is reported in up to 70% of cases. In contrast to EM major, the conjunctival process in KD lacks ulceration and significant discharge.
The orolabial mucosal surface also is frequently affected, and it too represents another "almost constant feature," of the disease, which presents within three days of fever onset with erythema of the pharynx and fissuring of the lips. (See Figures 4a and 4b.) The lips then become desiccated, complicated by further fissuring, while ulcerations may appear in an oropharyngeal distribution. The lingual papillae become hypertrophied, resulting in the "strawberry tongue" appearance similar to that seen in scarlet fever.
The rash, which is always erythematous and, frequently, polymorphous, is noted soon after onset of the fever. It resembles the dermatologic findings of EM with erythematous lesions of multiple form. The most frequently seen forms include a diffuse maculopapular eruption (see Figure 4b) and urticarial lesions. Perineal involvement is common, usually with erythematous maculopapules which then coalesce. Vesiculopapules are seen on the extensor surfaces of the large joints.
Desquamation occurs first in the perineal area followed by the distal extremities (See Figure 4c); diffuse skin loss is uncommon. Extremity changes include edema of the distal structures that may be so painful as to limit ambulation. Lymphadenopathy is seen in three-fourths of patents with KD. Firm, nontender lymph nodes are seen and may be limited to a single node.
Additional organ system involvement can be seen in the the heart, with coronary artery inflammation and aneurysmal formation, pericarditis, and myocarditis complicated by arrhythmias, myocardial infarction, and/or acute CHF. Cardiac involvement is seen in approximately 20% of children with KD, and is the major cause of mortality. KD-related death may also occur many years later due to sudden cardiac death or myocardial infarction, both of which may result from aneurysms. Aseptic meningitis, polyarthritis, urethritis, and hydrops of the gallbladder are also seen in the KD patient; the most frequent laboratory abnormality seen is thrombocytosis, which typically ranges from 600,000 to 1.5 million, and which appears on the 10th day of illness. Other laboratory findings include leukocytosis with left shift, alterations in the hepatic transaminases, sterile pyuria, and CSF pleocytosis. (See Table 5 for the differential diagnosis of KD.)
Table 6. Lesions of the Bullous Diseases
· Large, flaccid bulla
· Nikolski's sign
· Ulcers
· Exfoliation
· Mucous membrane involvement
Treatment. In addition to resuscitation and stabilization, the patient with suspected or confirmed KD should be admitted to the hospital for further diagnostic evaluation and monitoring of possible cardiac complications. Specific therapy includes aspirin and intravenous gamma globulin.
Bullous Diseases
Pemphigus Vulgaris & Bullous Pemphigoid. Of the autoimmune, "blistering" diseases, two-pemphigus vulgaris (PV) and bullous pemphigoid (BP)-are of importance to the emergency physician because of their severity, potential for rapid progression, and associated comorbidity.
PV is a generalized, mucocutaneous, autoimmune, blistering eruption with a grave prognosis. It is characterized by intraepidermal acantholytic blistering. Before the efficacy of systemic steroids in the treatment of pemphigus was noted in the 1950s, the disease had a one-year mortality rate of more than 90%. Today, only 10% of patients succumb to their disease, with most of these deaths resulting from immunosuppressive medication side-effects.26
BP is a generalized, mucocutaneous, blistering disease of the elderly, with an average age of 70 years at the time of initial diagnosis.27 Although the blisters are deeper in the skin than in PV (below the epidermal basement membrane), the prognosis is better. There is usually less associated comorbidity with a more rapid response to therapy.
Pathologically, both PV and BP are characterized by the presence of unique antigen/autoantibody systems. The presence of these autoantibodies may be detected using immunofluorescence techniques. PV is a prototypical autoimmune disease that, like Goodpasture's syndrome and myasthenia gravis, exhibits pathogenic autoantibodies. The autoimmune nature of PV was demonstrated by passive transfer experiments. These studies showed that the intraperitoneal administration of pemphigus IgG into neonatal Balb/c mice lead to blister formation with the histological, ultrastructural, and immunofluorescent features of PV.28 Although autoantibodies have been detected in BP, they have not been proven to be pathogenic. Recent research has identified the autoantigens in many of the autoimmune bullous diseases, and molecular genetics techniques have been used to clone the genes in BP and PV.29,30
Clinical presentation and diagnosis. The primary lesions of PV are vesicles or bullae that vary in diameter from less than 1 cm to several centimeters; they commonly first affect the head, trunk, and mucous membranes. The blisters are usually clear and tense, originating from normal skin or atop an erythematous or urticarial plaque. Within 2-3 days, the bullae become turbid and flaccid. Rupture soon follows, producing painful denuded areas. (See Figure 5a.) These erosions are slow to heal and are prone to secondary infection. Nikolski's sign is invariably positive in PV and absent in other autoimmune blistering diseases. (See Table 6 for the dermatologic lesions common to PV.)
Mucous membranes are affected in 95% of PV patients; in as many as 25% of these patients, the mucous membranes are the primary sites of involvement. Blisters on mucous membranes are more transitory than those on the skin in that they are more vulnerable to rupture; this is particularly true in the mouth, where ragged ulcerative lesions readily develop after inadvertent biting of the tissues. A few lesions will produce little discomfort, but extensive involvement of the tongue, cheeks, and oropharynx may be extremely painful-so painful that it interferes with the patient's alimentation and nutrition.
BP is characterized by the presence of tense blisters (up to 10 cm in diameter) that arise from either normal skin or from erythematous or urticarial plaques (see Figure 4b); ulceration with tissue loss follows. (See Figure 4c.) Sites of predilection include the intertriginous and flexural areas. Pruritis, occasionally accompanied by a burning sensation, is noted with the appearance of the blistering. Frank pain in the lesions is rarely present. (See Table 6 for the dermatologic lesions common to BP.)
Table 7. Differential Diagnosis of Bullous Diseases
· Toxic epidermal necrolysis
· Erythema multiforme
· Autoimmune blistering diseases
· Burns
· Severe contact dermatitis
· Bullous diabeticorum
· Friction blisters
Lesions of the oral cavity occur in BP, but with less consistency and severity than in PV. Because the blisters in the oral cavity rupture very easily and heal without scarring, involvement in the mouth is often overlooked. Oral involvement may occur in as many as 40% of patients.31 It is unusual for oral mucosal lesions to precede the cutaneous eruption as in PV, reported in only two of 36 patients in one series.32
The differential diagnosis of PV and BP (see Table 7) include all of those diseases that can present with primary skin blistering, including TEN, EM, other autoimmune blistering diseases, burns, severe contact dermatitis, bullous diabeticorum, and friction blisters. The nature of the clinical presentation, histology, and immunofluorescence testing should yield the correct diagnosis in the patient with generalized blistering.
Management. Limited oral intake and accelerated protein, fluid, and electrolyte losses through the involved skin can rapidly lead to hypoalbuminemia with significant hypovolemia and electrolyte disturbances in both PV and BP. Consequently, initial inpatient dermatological care is warranted in most cases with extensive blistering to initiate high-dose systemic steroid and immunosuppressive therapy.
Dermatological consultation is imperative at the time of the initial patient encounter in the ED. The cutaneous surfaces involved with blisters or eroded areas should be treated as burns with the application of silver sulfadiazine cream or antibiotic ointments with clean dressings. The pain originating from oral lesions may be partially relieved with soothing mouth washes (Cepacol [Marion Merrell Dow, Kansas City, MO] diluted 1:4 or 1:1 mixture of diphenhydramine elixir with Mylanta [Johnson & Johnson-Merck, Fort Washington, PA]) or with viscous lidocaine. Oral hygiene should be maintained via frequent mouth washes with normal saline or chlorhexidine gluconate (Peridex [Proctor and Gamble, Cincinnati, OH]) oral rinse solutions. Close observation and rapid treatment with appropriate antibiotics for superficial infection is imperative because the most frequent site for subsequent sepsis is the denuded cutaneous surface.
Currently, treatment with corticosteroids results in the complete recovery of some patients and control of the disease in others if the therapy is continued. Still, 10% of PV patients die either from the disease or complications of therapy, with adverse prognosis associated with the extent of disease at presentation and delay in treatment past six months from the onset. Ultimately, PV does remit. After a mean of 8.7 years in a cohort of PV patients, 45% were free of disease and off of therapy, and 38% were clinically free of disease on low-dose maintenance steroid therapy.33
BP is also managed by systemic steroids, especially when there is widespread disease. Mild disease, arbitrarily defined as less than 20 lesions, usually responds to lower doses of steroids, (e.g., 20-40 mg of prednisone per day). BP had a 25% mortality rate before the introduction of steroid treatment. Today, patients with BP usually recover from the disease, although treatment may be necessary for months and even years. In one series, 16% of patients were still under active treatment for their disease after three years.33 Complications from systemic therapy with corticosteroids and immunosuppressants have special hazards to be considered in treating elderly patients with concomitant disease, including diabetes, hypertension, and glaucoma.34
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