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CHAPTER 249: Generalized Skin Disorders 1623 wet cutaneous syndromes involve similar protein and lipid losses due to excessive flow of transudative or exudative fluid from the diseased skin with leaching of the complex macromolecules of the epithelial cells. Drying agents retard this flow of fluid and associated biologic materials from the body, thus assisting in the curative process. Capsaicin, a topical agent derived from chili peppers that affects the release of substance P , can desensitize local nerve fibers and has been recommended as an antipruritic agent. 14 A topical preparation of 0.025% three times a day for up to 4 weeks is well tolerated by most patients. Capsaicin is not recommended for patients under 10 years of age. Topical local anesthetic treatments such as pramoxine 1% or 2.5% or the mixture of lidocaine and 2.5% cream have been reported in case series to improve pruritus; however, studies with high level of evidence are lacking, and the long-term safety profile is unknown. Topical Agent Medication Base (Vehicle) The vehicle, or medication base, is the substance in which the active ingredient is dispersed. The base determines the rate at which the active ingredient is absorbed through the skin. Components of some bases may cause irritation or allergy. Creams, a mixture of oils, water, and preservative, are white and greasy in texture. Creams are the most versatile vehicle and can be applied to any body surface area. They are particularly useful in the intertriginous areas. Creams are best used for acute therapy only; chronic application may cause excessive drying. Some patients are allergic to the preservatives in creams; in these patients, consider switching to an ointment preparation of the medication. Ointments are composed of greases such as petroleum jelly and are free of preservative. Little water is added to this vehicle. Ointments are translucent and, when applied to the skin, remain greasy. This greasy consistency lubricates particularly dry lesions. In general, ointment vehicles allow deeper tissue penetration compared with cream bases. Ointments also are occlusive, providing very thorough coverage with deep tissue penetration and allowing little movement in moisture and other material into and out of the skin. Acute exudative syndromes and intertriginous areas of the body should not be treated with topical ste roids formulated using an ointment vehicle. Gels are greaseless mixtures of propylene glycol and water and at times contain alcohol. Gels have a translucent appearance and are described as “sticky. ” Alcohol-containing gels are best for acute exudative lesions, such as poison ivy dermatitis, whereas alcohol-free combinations should be used for dry, scaling conditions. In denuded areas, the alcohol component may cause discomfort. Gels are sometimes preferred for the scalp, because they do not alter the hairstyle and are cosmetically tolerable. Solutions or lotions may contain water or alcohols in addition to other agents. They are clear or milky in appearance and are most useful for the scalp and other dense hair-bearing areas because they leave no significant residue on the hair. In denuded areas, the alcohol component may cause discomfort. Some topical steroids are available as foams. Clobetasol (a very potent topical steroid) is safe and effective as a foam. It is important to note that the absorption rate of clobetasol is greater for the foam vehicle formulation than for the topical solution.

n denuded areas, the alcohol component may cause discomfort. Some topical steroids are available as foams. Clobetasol (a very potent topical steroid) is safe and effective as a foam. It is important to note that the absorption rate of clobetasol is greater for the foam vehicle formulation than for the topical solution. Topical Agent Toxicity Topical agents with certain active ingredients must be used with caution. These ingredients are often very effective, but the delivery is uncontrolled. Although the patient can control the amount and frequency of application, the actual amount of systemic absorption is not easily managed. For instance, certain agents are well absorbed through normal skin and mucous membranes, whereas other medications are absorbed only through irritated skin or mucosa. Topical formulations containing agents absorbed through irritated skin include the Lidoderm patch (containing lidocaine), Caladryl lotion (containing pramoxine, a local anesthetic), Bengay  (containing methyl salicylate), and Icy Hot  (containing menthol and methyl salicylate). Reports of significant toxicity, including death, have been reported with these and similar agents when excessively applied topically. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Generalized Skin Disorders William J. Brady Amit Anil Kumar Pandit Mark R. Sochor INTRODUCTION This chapter describes selected serious generalized skin disorders in adults and discusses their dermatologic diagnosis and treatment. Cov ered are erythema multiforme, toxic epidermal necrolysis, exfoliative erythroderma, the toxic infectious erythemas, disseminated viral infec tions, Rocky Mountain spotted fever, disseminated gonococcal infection, purpura fulminans, and pemphigus vulgaris. Staphylococcal scalded skin syndrome and meningococcemia are discussed in the pediatric section, in Chapter 142, “Rashes in Infants and Children. ” Disseminated viral infections are discussed in Chapter 154, “Serious Viral Infections” and in Chapter 142. The disorders erythema multiforme, toxic epidermal necrolysis, exfoliative erythroderma, staphylococcal and streptococcal toxic shock syndrome, and staphylococcal scalded skin syndrome share some fea tures in common. Table 249-1 can help to differentiate these disorders. Management is summarized in Table 249-2. ERYTHEMA MULTIFORME Erythema multiforme is an acute inflammatory skin disease (Figure 249-1) that ranges from a minimal, nuisance-level event to a severe multisystem illness. It is divided into two distinct subtypes, considering the extent of involvement, presence of epidermal detachment, and the development of mucous membrane lesions. Erythema multiforme minor is a localized papular eruption of the skin, with an acral distribution and involving target lesions and/or raised, edematous papules. Erythema multiforme major is the severe form with multisystem involvement and widespread vesiculobullous lesions and erosions of the CHAPTER TABLE 249-1 Comparison of Inflammatory and Infectious Generalized Skin Disorders Disorder Appearance Special Features Erythema multiforme Erythematous macules, papules Target lesions Urticaria or vesiculobullous lesions Cutaneous reaction to drugs or infectious agents. Stevens-Johnson syndrome is the most severe form. Toxic epidermal necrosis Painful, tender erythroderma Vesicles and bullae Exfoliation Nikolsky sign present. Stevens-Johnson syndrome is most severe form. Drugs most common cause. Exfoliative erythroderma Nontender erythema Skin flaking and scaling Thickening of skin Often preexisting eczema or psoriasis; can be drug induced.

pidermal necrosis Painful, tender erythroderma Vesicles and bullae Exfoliation Nikolsky sign present. Stevens-Johnson syndrome is most severe form. Drugs most common cause. Exfoliative erythroderma Nontender erythema Skin flaking and scaling Thickening of skin Often preexisting eczema or psoriasis; can be drug induced. Staphylococcal or streptococcal toxic shock syndrome Staphylococcal: fine punctate erythematous lesions that become confluent; blanching erythroderma; desquamation first of trunk and face, then extremities Streptococcal: can be indistinguishable from staphylococcal toxic shock; scarlatiniform erythroderma with sheet-like desquamation of skin Colonization or infection with Staphylococcus aureus; menstruation associated with tampon use; nonmenstrual associated with burns, cellulites, sinusitis, wounds, etc. Group A streptococcal cellulitis, puerperal sepsis, any group A β-hemolytic Streptococcus infection source. Staphylococcal scalded skin syndrome Scarlatiniform rash or erythema Bullae or bullous impetigo Sloughing of skin Usually seen in neonates or children <5 y of age. Nikolsky sign present. Tintinalli_Sec20_p1607-1668.indd 1623 8/2/19 7:24 PM

litis, puerperal sepsis, any group A β-hemolytic Streptococcus infection source. Staphylococcal scalded skin syndrome Scarlatiniform rash or erythema Bullae or bullous impetigo Sloughing of skin Usually seen in neonates or children <5 y of age. Nikolsky sign present. Tintinalli_Sec20_p1607-1668.indd 1623 8/2/19 7:24 PM 1624 SECTION 20: Dermatology TABLE 249-2 Management of Serious Generalized Skin Disorders Disorder Treatment Disposition/Comments Erythema multiforme minor •  Steroid  (prednisone 60–80 milligrams PO daily for 3–5 d or equivalent) •  Oral antihistamine (diphenhydramine 25–50 milligrams every 4–6 h or equivalent) •  Acyclovir for herpes simplex virus–related event (recurrence suppression only) •  Remove  trigger if identified •  Outpatient  management •  Primary  care physician or dermatology follow-up Erythema multiforme major (Stevens-Johnson syndrome) •  Resuscitate  as needed (respiratory +/– circulatory) •  Fluid  and electrolyte management as needed •   Steroid (as above or methylprednisolone 125 milligrams IV every 6 h or equivalent)* •  Pain  management as appropriate •  Diphenhydramine  and viscous lidocaine rinses for oral lesions •  Burow’s  solution (5% aluminum acetate) with cool compresses for blisters •  Ophthalmologist  for ocular lesions •  Antibiotic  only for suspected or established infection (i.e., not prophylactic) •  Remove  trigger if identified •  Inpatient  management; acute, critical care, or burn unit •  Intensivist † and dermatologist consultations Toxic epidermal necrosis •  Resuscitate  as needed (respiratory +/– circulatory) •  Fluid  and electrolyte management as needed •  Antibiotic  only for suspected or established infection (i.e., not prophylactic) •  Remove  trigger if identified •  Inpatient  management, critical care or burn unit •  Intensivist † and dermatologist consultations Pemphigus vulgaris •  Resuscitate  as needed (respiratory +/– circulatory) •  Fluid  and electrolyte management as needed •  Antibiotic  only for suspected or established infection (i.e., not prophylactic) •  Immunosuppressive  therapy* •  Plasmapheresis* •  Immunoglobulin  therapy* •  Inpatient  management; acute, critical care, or burn unit •  Intensivist † and dermatologist consultations Exfoliative dermatitis minor •  Remove  trigger if identified •  Symptomatic  care (oral pain and antihistamine agents as needed [PRN]) •  Outpatient  management •  Primary  care physician or dermatology follow-up Exfoliative dermatitis major •  Resuscitate  as needed (circulatory) •  Correct  hypothermia •  Remove  trigger if identified •  Symptomatic  care (oral pain and antihistamine agents PRN) •   Steroid after dermatologist consultation (methylprednisolone 125 milligrams IV every 6 h or equivalent)* •  Inpatient  management; acute, critical care, or burn unit •  Intensivist † and dermatologist consultations DRESS (drug rash with eosinophilia and systemic symptoms) syndrome •  Resuscitate  as needed (respiratory +/– circulatory) •  Remove  trigger if identified •  Symptomatic  care (oral pain and antihistamine agents PRN) •  Antipyretic  therapy •  Steroid (as above or methylprednisolone 125 milligrams IV every 6 h or equivalent)* •  Inpatient  management, acute or critical care unit •  Intensivist † and dermatologist consultations Staphylococcal toxic shock syndrome •  Resuscitate  as needed (respiratory +/– circulatory) •  Removal of foreign body source (usually colonization only, not active infection) •  Antistaphylococcal  antibiotics (only reduces recurrence) •  Inpatient  management, acute or critical care unit •  Intensivist, † infectious disease, and dermatologist PRN Streptococcal toxic shock syndrome •  Resuscitate  as needed (respiratory +/– circulatory) •  Broad-spectrum  antibiotics with antistreptococcal coverage •   At

coccal  antibiotics (only reduces recurrence) •  Inpatient  management, acute or critical care unit •  Intensivist, † infectious disease, and dermatologist PRN Streptococcal toxic shock syndrome •  Resuscitate  as needed (respiratory +/– circulatory) •  Broad-spectrum  antibiotics with antistreptococcal coverage •   At tention to soft tissue infection with incision/drainage, debridement, amputation, etc. •  Inpatient  management, acute or critical care unit •  Intensivist, † infectious disease, surgeon, and dermatologist PRN Staphylococcal scalded skin syndrome •  Resuscitate  as needed (respiratory +/– circulatory) •  Fluid  and electrolyte management as needed •  Identification  of source (colonization or active infection) •  Antistaphylococcal  antibiotics •  Topical  dressings PRN* •  Inpatient  management, acute or critical care unit •  Intensivist, † infectious disease, and dermatologist PRN Meningococcemia •  Resuscitate  as needed (respiratory +/– circulatory) •  Parenteral  antibiotics •  Critical  care unit •  Intensivist Purpura fulminans •  Resuscitate  as needed (respiratory +/– circulatory) •  Critical  care unit •  Intensivist *Therapy guided by dermatologist. †Intensivist involvement if patient admitted to critical care unit. Tintinalli_Sec20_p1607-1668.indd 1624 8/2/19 7:24 PM

al  antibiotics •  Critical  care unit •  Intensivist Purpura fulminans •  Resuscitate  as needed (respiratory +/– circulatory) •  Critical  care unit •  Intensivist *Therapy guided by dermatologist. †Intensivist involvement if patient admitted to critical care unit. Tintinalli_Sec20_p1607-1668.indd 1624 8/2/19 7:24 PM CHAPTER 249: Generalized Skin Disorders 1625 mucous membranes; specifically, erythema multiforme major includes involvement of one or more mucous membrane areas and epidermal detachment less than 10% of total body surface area. Some authorities include Stevens-Johnson syndrome as a severe form of erythema mul tiforme major, whereas others consider it a less severe form of toxic epidermal necrolysis. Perhaps the most appropriate classification approach for the emergency provider is as follows: Stevens-Johnson syndrome presents with less than 10% of the body surface area with epidermal detachment; the “overlap” presentation of Stevens-Johnson syndrome and toxic epidermal necrolysis presents with 10% to 30% epidermal detachment; and toxic epidermal necrolysis presents with greater than 30% epidermal detachment. 1 In either consideration, Stevens-Johnson syndrome is a serious dermatologic illness with significant, widespread skin involvement, more extensive epidermal detachment, and mucous membrane lesions. This taxonomic controversy has no meaning for the emergency clinician; what is important is the recognition of a sig nificant, potentially life-threatening, multisystem dermatologic condition. Morbidity and mortality rise with the amount of epidermal detachment. The highest incidence is in young adults (age range, 20 to 40 years), and erythema multiforme occurs commonly in the spring and fall. Common precipitating factors are infection, especially with Mycoplasma and herpes simplex virus; drugs, especially antibiotics and anticonvul sants; and malignancies. However, the cause is often unknown. 3 Most likely, erythema multiforme is the result of a hypersensitivity reaction, with immunoglobulin and complement components demonstrated in the cutaneous microvasculature on immunofluorescent studies of skin biopsy specimens, circulating immune complexes found in the serum, and mononuclear cell infiltrate noted on histologic examination. 3,4 Symptoms include malaise, fever, myalgias, and arthralgias. Diffuse pruritus or a generalized burning sensation can occur before the skin lesions develop. The morphologic configuration of the lesions is vari able, hence the descriptor multiforme. Maculopapular ( Figure 249-2) and target, or iris ( Figure 249-3), lesions are the most characteristic. Erythematous papules appear symmetrically on the dorsum of the hands and feet and on the extensor surfaces of the extremities. The maculopapule evolves into the classic target lesion during the next 24 to 48 hours. As the maculopapule enlarges, the central area becomes cyanotic, occa sionally accompanied by central purpura or a vesicle. Urticarial plaques also may occur with or without the iris lesion in a similar distribution. Vesiculobullous lesions, which may be pruritic and painful, develop within preexisting maculopapules or plaques, usually on the extensor surface of the arms and legs and less frequently on the trunk. Vesiculobullous lesions are found most often on mucosal surfaces, including the mouth, eyes, vagina, urethra, and anus; they may also be seen on the FIGURE 249-1. Erythema multiforme. FIGURE 249-2. Maculopapular erythema multiforme. trunk. Ocular involvement rarely occurs in erythema multiforme minor, whereas ophthalmologic lesions are seen in almost 70% of patients with Stevens-Johnson syndrome. 5 The various lesions ( Table 249-3) develop in successive crops during a 2- to 4-week period and heal over 5 to 7 days.

culopapular erythema multiforme. trunk. Ocular involvement rarely occurs in erythema multiforme minor, whereas ophthalmologic lesions are seen in almost 70% of patients with Stevens-Johnson syndrome. 5 The various lesions ( Table 249-3) develop in successive crops during a 2- to 4-week period and heal over 5 to 7 days. The differential diagnosis of erythema multiforme includes herpetic (herpes simplex virus and varicella-zoster virus) infection, vasculitis, toxic epidermal necrolysis, various primary blistering disor ders (pemphigus and pemphigoid), urticaria, Kawasaki’s disease, and the toxic and infectious erythemas. Recurrence may be noted on repeat exposure to the etiologic agent, a special concern in cases associated with herpes simplex virus infection or medication use. 6 The rate of erythema multiforme recurrence is very FIGURE 249-3. Target, or iris, lesions of erythema multiforme. [Photograph used with permission of Kenneth Greer, MD, University of Virginia Dermatology.] Tintinalli_Sec20_p1607-1668.indd 1625 8/2/19 7:24 PM

ated with herpes simplex virus infection or medication use. 6 The rate of erythema multiforme recurrence is very FIGURE 249-3. Target, or iris, lesions of erythema multiforme. [Photograph used with permission of Kenneth Greer, MD, University of Virginia Dermatology.] Tintinalli_Sec20_p1607-1668.indd 1625 8/2/19 7:24 PM 1626 SECTION 20: Dermatology FIGURE 249-4. Toxic epidermal necrolysis. high in children with herpes simplex virus infection. For example, 75% of children with a history of herpes simplex virus–related erythema multiforme developed erythema multiforme recurrence after herpes simplex virus reactivation. 6 Fluid and electrolyte disorders and secondary infec tion from cutaneous sites are the most frequent complications. Treatment is provided in Table 249-2. Systemic steroids are com monly used for localized disease and provide symptomatic relief, but are of unproven benefit in influencing the duration and outcome of erythema multiforme. 7 Many authorities recommend a short, intensive steroid course of prednisone, 60 to 80 milligrams PO once a day, par ticularly in drug-related cases, with abrupt cessation in 3 to 5 days if no favorable response is noted. Unfortunately, burst steroid therapy does not reduce the chance of development or significance of existing ocular lesions. Provide symptomatic relief of stomatitis and blisters. Do not swallow oral viscous lidocaine because it causes neurotoxicity. Consult ophthalmology for ocular involvement. Acyclovir may reduce recur rence of herpes simplex virus infection and therefore lessen the potential for another bout of erythema multiforme; prolonged prophylactic acy clovir therapy may reduce the chance of recurrent erythema multiforme related to herpes simplex virus. TOXIC EPIDERMAL NECROLYSIS Toxic epidermal necrolysis (Figure 249-4) is an explosive dermatosis characterized by tender erythema, bullae formation, mucous membrane lesions, and subsequent exfoliation. Patients are systemically ill. Many authorities consider Stevens-Johnson syndrome to be a less severe form of toxic epidermal necrolysis, whereas others consider Stevens-Johnson syndrome to be a more severe form of erythema multiforme major; in either case, Stevens-Johnson syndrome and toxic epidermal necrolysis are severe dermatologic illnesses, whether they are distinct entities or two forms of the same syndrome. Toxic epidermal necrolysis is found in all age groups without predi lection for either sex. The syndrome has multiple causes, with medica tions being the most common cause. 3,4,8 Sulfa and penicillin antibiotics, anticonvulsants, and oxicam NSAIDs are the most frequent drug trig gers for toxic epidermal necrolysis.9,10 Other causes include malignancy and human immunodeficiency virus infection. 8,11,12 In many cases, a cause is not found. The pathogenesis is poorly understood and may be partly immunologic and partly genetic. Symptoms include a 1- to 2-week prodrome of malaise, anorexia, arthralgias, fever, or symptoms of upper respiratory tract infection. Skin tenderness, pruritus, tingling, or burning may be found at this time. Skin signs (Table 249-3) begin with a warm erythema, initially involving only the eyes, nose, mouth, and genitalia, but later becoming generalized. The erythematous areas become tender and confluent within hours. Flaccid, ill-defined bullae then appear within the areas of erythema. Lateral pressure with a finger on normal skin adjacent to a bullous lesion dislodges the epidermis, producing denuded dermis and demonstrating Nikolsky sign. Nikolsky sign is slippage of the epidermis from the dermis when slight rubbing pressure is applied to the skin. The bullae form along the cleavage plane between the epidermis and the dermis.

er on normal skin adjacent to a bullous lesion dislodges the epidermis, producing denuded dermis and demonstrating Nikolsky sign. Nikolsky sign is slippage of the epidermis from the dermis when slight rubbing pressure is applied to the skin. The bullae form along the cleavage plane between the epidermis and the dermis. The epidermis is then shed in large sheets, which leaves raw, denuded areas of exposed dermis. The average time until onset after exposure to the inciting agent is 2 weeks. Cutaneous extension follows an unpredictable time course, ranging from 24 hours to 15 days, with some severe cases demonstrating rapid, extensive involvement within 24 hours. Perilabial blistering and erosive lesions are disfiguring and often impair adequate oral intake, contributing to hypovolemia. Ocular complications include purulent conjunctivitis, painful erosions, and potential blindness. Anogenital lesions are common. Additional mucous membrane involvement includes the GI, urinary, and respiratory tracts. The two major complications and leading causes of death in toxic epidermal necrolysis are infection and hypovolemia with electrolyte disorders. A broad range of pathogens is usually found, with staphylococcal and pseudomonal species predominating. The mortality rate is as high as 30%. 8 The clinical characteristics associated with poor prognosis include advanced age, extensive disease, idiopathic nature, use of multiple medications, steroid therapy, azotemia, hyperglycemia, leukopenia, and thrombocytopenia. The differential diagnosis of toxic epidermal necrolysis is presented in Table 249-1 and also includes primary blistering disorders (pemphigus and pemphigoid) and Kawasaki’s disease in children. Treatment is presented in Table 249-2. Toxic epidermal necrolysis requires hospitalization in an intensive care or burn unit. 9 Immediate concerns center on the airway, because sloughing of airway and respiratory epithelium can occur. Hypovolemia and electrolyte abnormalities should be corrected. Prompt, aggressive antibiotic administration is necessary in suspected or documented infection; initial prophylactic antibiotics are not recommended by most. Solicit the advice of the burn center regarding any topical dressings that are applied before transfer. TABLE 249-3 Erythema Multiforme and Toxic Epidermal Necrolysis Lesions of Erythema Multiforme Lesions of Toxic Epidermal Necrolysis Erythematous maculopapules Warm, tender erythroderma Iris or target lesions Vesicles and bullae Urticaria Exfoliation Mucous membranes involved Mucous membranes involved Tintinalli_Sec20_p1607-1668.indd 1626 8/2/19 7:24 PM

d Toxic Epidermal Necrolysis Lesions of Erythema Multiforme Lesions of Toxic Epidermal Necrolysis Erythematous maculopapules Warm, tender erythroderma Iris or target lesions Vesicles and bullae Urticaria Exfoliation Mucous membranes involved Mucous membranes involved Tintinalli_Sec20_p1607-1668.indd 1626 8/2/19 7:24 PM CHAPTER 249: Generalized Skin Disorders 1627 PEMPHIGUS VULGARIS Pemphigus vulgaris is a generalized, mucocutaneous, autoimmune, blistering eruption with a grave prognosis characterized by intraepi dermal acantholytic blistering (Table 249-4). The primary lesions of pemphigus vulgaris are vesicles or bullae ( Figure 249-5) that vary in diameter from <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 to 3 days, the bullae become turbid and flaccid. Rupture soon follows, producing painful, denuded areas. These erosions are slow to heal and prone to secondary infection. The Nikolsky sign is present in pemphigus vulgaris. Mucous membranes are affected in most patients, and in some, the mucous membranes are the primary sites of involvement. Blisters on mucous membranes are more transitory than blisters 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. Bullous pemphigoid, another mucocutaneous blistering disorder, can present in similar fashion to pemphigus vulgaris with the following significant differences found in the bullous pemphigoid: older average age at onset, larger blister size, lower rate of mucous membrane involvement, and overall “less toxicity” with better outcome. Limited oral intake and accelerated protein, fluid, and electrolyte losses through the involved skin can rapidly lead to hypovolemia and electrolyte disturbances. Treatment is provided in Table 249-2. EXFOLIATIVE DERMATITIS Exfoliative dermatitis is a condition in which most or all of the skin surface is involved with a scaly erythematous dermatitis. It is a cutaneous reaction in response to a drug or a chemical agent or to an underlying systemic or cutaneous disease. Most patients are over 40 years of age. The cause is unknown. Exfoliative dermatitis can have an abrupt onset, particularly when related to a drug, 13,14 contact allergen, or malignancy; exacerbations related to an underlying cutaneous disorder usually evolve more slowly. Exfoliative dermatitis tends to be a chronic condition, with a mean duration of TABLE 249-4 Characteristics of Pemphigus Vulgaris Lesions •  Large,  flaccid bullae •  Nikolsky  sign present •  Skin  ulcerations •  Exfoliation •  Mucous  membrane involvement 5 years, when related to a chronic illness; the course is often shorter after suppression of the underlying dermatosis, discontinuation of causative drugs, or avoidance of allergen. Idiopathic and chronic disease–related exfoliative dermatitis can continue for ≥20 years; death is rare. Generalized erythema and warmth are noted, but skin tenderness is usually lacking. Erythema is accompanied by scaling or flaking, and the patient often complains of pruritus and skin tightness (Figure 249-6). The process generally begins on the face and upper trunk with progres sion to other skin surfaces. The patient usually has a low-grade fever. Excessive heat loss and hypothermia can complicate exfoliative derma titis. Widespread cutaneous vasodilation may result in high-output congestive heart failure. The disruption of the epidermis results in increased transepidermal water loss, and continued exfoliation can result in significant protein loss and negative nitrogen balance.

ss and hypothermia can complicate exfoliative derma titis. Widespread cutaneous vasodilation may result in high-output congestive heart failure. The disruption of the epidermis results in increased transepidermal water loss, and continued exfoliation can result in significant protein loss and negative nitrogen balance. Chronic inflammatory exfoliation produces many changes, such as dystrophic nails, thinning scalp and body hair, and patchy or diffuse pigmentation changes. The differential diagnosis is found in Table 249-1, and treatment is provided in Table 249-2. Patients generally require admission. Correct hypothermia and hypovolemia. Obtain dermatology consultation before giving systemic corticosteroids. DRESS (DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS) SYNDROME Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug reaction that usually develops within 8 weeks of initiation of drug therapy. Aromatic anticonvulsants (such as phenytoin and phenobarbital), allopurinol, and sulfa medications are the most common culprits; however, other causes include NSAIDs, antiretroviral medications, angiotensin-converting enzyme inhibitors, calcium channel blockers, and other antibiotics. 13-16 It is believed that there is a genetic predisposition if exposed to the appropriate medication.15 Because of the potential genetic risk, DRESS syndrome risks and implications should be discussed with the family members of any patient in whom it is diagnosed. DRESS syndrome is defined by fever, rash, and internal organ involvement, with the liver, kidneys, and hematologic system being most commonly affected. 15 Rash and fever are typically the first signs of the syndrome, and they may have associated lymphadenopathy (Figure 249-7). The rash itself can take multiple forms, ranging from an erythematous scaly rash similar to that of exfoliative dermatitis, to a blistering/bullous rash similar to that of Stevens-Johnson syndrome, with varying degrees of severity. Abnormal laboratory findings include eosinophilia, which occurs in about 30% of DRESS syndrome patients, 17 and hepatic and renal dysfunction. Because of the variety of clinical presentations, early diagnosis of DRESS syndrome is difficult and requires a high level of clinical suspicion. The current treatment FIGURE 249-5. Scattered bullous lesions intermixed with erosions and painful inflam matory plaques in a patient with pemphigus vulgaris. FIGURE 249-6. Exfoliative dermatitis demonstrated by generalized, warm erythema accompanied by scaling or flaking. Tintinalli_Sec20_p1607-1668.indd 1627 8/2/19 7:24 PM

rrent treatment FIGURE 249-5. Scattered bullous lesions intermixed with erosions and painful inflam matory plaques in a patient with pemphigus vulgaris. FIGURE 249-6. Exfoliative dermatitis demonstrated by generalized, warm erythema accompanied by scaling or flaking. Tintinalli_Sec20_p1607-1668.indd 1627 8/2/19 7:24 PM 1628 SECTION 20: Dermatology FIGURE 249-9. Purpura fulminans (A) with early skin necrosis and ( B) later with hemorrhagic bullae. [Photographs used with permission of Kenneth Greer, MD, University of Virginia Dermatology.] FIGURE 249-7. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome caused by phenytoin. FIGURE 249-8. Early findings of meningococcemia with petechiae evolving into pru ritic lesions. [Photograph used with permission of Kenneth Greer, MD, University of Virginia Dermatology.] (Table 249-2) involves immediate stoppage of the suspected culprit medication, administration of systemic steroids in severe cases (those with evidence of hepatitis, pneumonitis, or extensive exfoliative dermatitis), supportive care including antipyretic and antipruritic medications, and hospital admission. 17,18 PURPURIC DISORDERS  MENINGOCOCCEMIA Meningococcemia is a potentially fatal infectious illness caused by the gram-negative diplococcus Neisseria meningitidis. Meningococcal disease presents across a wide clinical spectrum in the acute and chronic forms. The acute entities include pharyngitis, meningitis, and bactere mia. Meningococci are present in mucosal samples from approximately 5% to 10% of the general population (the carrier state). 19,20 In high-risk populations, such as military recruits, the organism may be found in almost half of people without evidence of active disease. The illness usually strikes patients <20 years of age, with the vast majority of cases occurring in children and infants <5 years old. A rash is frequently noted on presentation and is an invaluable clue to the correct diagnosis early in the disease course. The dermatologic mani festations include petechiae, urticaria, hemorrhagic vesicles, macules, and/or maculopapules (Figure 249-8). The classic 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, a pathognomic finding for menin gococcal infection. The skin findings result from the organism’s invasion and destruction of the endothelium. Histopathologic analysis shows an infectious vasculitis. For further discussion, see Chapters 142, “Rashes in Infants and Children, ” and 120, “Meningitis in Infants and Children. ”  PURPURA FULMINANS Purpura fulminans is a rare vascular disorder characterized by fever, shock, multiorgan failure, and the rapid development of hemorrhagic skin necrosis. It is associated with dermal vascular thrombosis, vas cular collapse, and disseminated intravascular coagulation. Purpura fulminans can result from hereditary or acquired protein C deficiency, activated protein C resistance, or protein S deficiency. It may also result from any condition that causes disseminated intravascular coagulation. Purpura fulminans presents with the dermatologic triad of wide spread ecchymoses, hemorrhagic bullae ( Figure 249-9), and epidermal necrosis. Cyanosis with initial ecchymoses and ultimate necrosis of the tip of the nose, ears, and genitalia frequently occur; in general, distal Tintinalli_Sec20_p1607-1668.indd 1628 8/2/19 7:24 PM