 |
|||||||||
|
|||||||||
| CECIL |
| TEXT BOOK of MEDICINE |
Section XXVIII Skin Diseases
| 465 MACULAR, PAPULAR, VESICULOBULLOUS, AND PUSTULAR DISEASES Neil J. Korman • |
|
|
▪MACULAR AND PAPULAR EXANTHEMS
An exanthem is an acute generalized eruption of the skin, and there are two major types: scarlatiniform eruptions and morbilliform eruptions. Scarlatiniform eruptions consist of confluent blanching erythema; their name was derived from their similarity to the eruption of scarlet fever (Table 465-1). Morbilliform eruptions consist of erythematous macules and papules; they are named for their resemblance to the measles eruption. Morbilliform eruptions can be caused by exposure to medications (Chapter 466) or viral infections.
Click here to view this table….
▪Scarlatiniform Eruptions
▪ Scarlet Fever
Scarlet fever is caused by infection of the ears, nose, throat, and skin with toxin-producing β-hemolytic streptococci (Chapter 312). It most commonly occurs in children after streptococcal wound infections, burns, and upper respiratory tract infections. Occasional cases of scarlet fever can also be caused by Staphylococcus aureus (Chapter 310), Haemophilus influenzae (Chapter 323), and Clostridium species (Chapter 319). The rash is due to a circulating toxin that induces local production of inflammatory mediators and alteration of cutaneous cytokines. Patients may have an abrupt onset of fever, headache, vomiting, malaise, chills, and sore throat. The mucous membranes are usually erythematous with petechiae, and the tongue commonly has a white membrane. Red, exudative tonsils are present with pharyngeal infections. The skin eruption appears after the fever and is characterized by fine erythematous papules, first on the upper part of the trunk and then in a more general distribution. The face is flushed, and circumoral pallor is seen. This eruption lasts for 4 to 5 days, followed by fine desquamation, the extent and duration of which are related to the severity of the eruption. Treatment is 1.2 million units of benzathine penicillin G given intramuscularly or oral penicillin VK, 1000 mg twice daily for 10 days. Most patients recover after 4 to 5 days, and the rash usually resolves completely over a period of several weeks.
▪ Toxic Shock Syndrome
Definition
Toxic shock syndrome is an acute febrile illness caused by toxin-producing strains of S. aureus (Chapter 310) or, less commonly, Streptococcus (toxic shock–like syndrome [Chapter 311]).
Pathobiology
Most cases of staphylococcal toxic shock syndrome or streptococcal toxic shock–like syndrome occur in young healthy persons aged 20 to 50 years. These toxins cause massive release of tumor necrosis factor-α and interleukin-1, cytokines that mediate fever, rash, hypotension, tissue injury, and shock.
Clinical Manifestations
The hallmarks of the disease are fever, rash, hypotension, and involvement of multiple organs, including the lungs, kidneys, liver, and gastrointestinal tract. Desquamation of the palms and soles follows onset of the illness by 1 to 2 weeks. There is diffuse macular erythema with flexural accentuation, mucous membrane erythema, and severe conjunctival involvement. Blood cultures are positive in 5 to 15% of patients with staphylococcal toxic shock syndrome and approximately 50% of those with streptococcal toxic shock–like syndrome.
Treatment
Treatment is supportive and includes hydration, vasopressors, appropriate antibiotics, and drainage of infected sites. Patients with staphylococcal toxic shock should be treated with intravenous vancomycin to cover methicillin-resistant staphylococci, 1 g every 12 hours for 10 to 15 days, with dose adjustment based on creatinine clearance. Patients with streptococcal toxic shock should be treated with both intravenous penicillin G, 3 to 4 million units every 4 hours, and intravenous clindamycin, 600 to 900 mg every 8 hours for 10 to 15 days, followed by oral therapy. Double antibiotic coverage is the standard of care for streptococcal toxic shock syndrome because this infection is characterized by extremely large numbers of stationary bacteria and penicillin alone is not effective in this scenario inasmuch as penicillin binding proteins are not expressed during the stationary group phase of streptococci. Silver sulfadiazine cream may lead to increased toxin production; therefore, mupirocin ointment should be used for infected sites.
Prognosis
The mortality rate in patients with staphylococcal toxic shock syndrome is 5 to 15%, whereas that for streptococcal toxic shock–like syndrome may be five times higher.
Kawasaki's Disease
Epidemiology
Kawasaki's disease, a systemic vasculitis of unknown etiology, occurs in children of all races but is most prevalent in Japan. Though primarily an illness of children younger than 5 years, Kawasaki's disease also occurs in adults. Its epidemiologic and clinical manifestations imply that an infection is the cause, but bacterial, viral, and serologic studies have yet to confirm such an etiology.
Clinical Manifestations
The clinical hallmarks are fever lasting up to 2 weeks, with spikes to 40° C (104° F), and a toxic-appearing patient. During the acute phase, the polymorphic eruption may be scarlatiniform, urticarial, morbilliform, or targetoid. Desquamation occurs in the perianal area 2 days after the onset of fever and on the extremities 2 to 3 weeks later. Patients often have hemorrhagic, dry fissured lips, conjunctival injection, a “strawberry tongue,” and cervical lymphadenitis. Myocarditis and coronary artery aneurysms may develop in untreated patients, so prompt diagnosis is critical. Other findings include arthralgias and arthritis, urethritis, aseptic meningitis, pneumonitis, and diarrhea.
Diagnosis
Despite the lack of specific diagnostic tests for this syndrome, the typical skin eruption accompanied by myocarditis is characteristic.
Treatment
Recommended therapy in the acute phase includes intravenous gamma globulin, 400 mg/kg/day for 4 days, and acetylsalicylic acid, 100 mg/kg, until the patient has been afebrile for several days. During the subacute and convalescent phase, acetylsalicylic acid is usually given at 3 to 8 mg/kg for 6 to 8 weeks. The optimal salicylate regimen for Kawasaki's disease remains uncertain, and there are no controlled trials to prove that aspirin reduces coronary artery aneurysms.
▪Morbilliform Eruptions
▪ Measles
Measles is caused by a paramyxovirus (Chapter 390) that infects respiratory epithelium and is highly transmissible. The incubation period is 7 to 14 days. The prodrome consists of cough, coryza, and conjunctivitis. The enanthem, or Koplik's spots, predates the exanthem by 1 to 2 days and lasts 2 to 4 days. These blue-white spots surrounded by a red halo appear on the buccal mucosa and are pathognomonic for measles. The exanthem begins on the fourth or fifth day as papules on the face and behind the ears; it then spreads to the trunk and extremities. Measles is diagnosed on clinical grounds. Active immunization with live attenuated virus has dramatically reduced the incidence of measles infection (Chapter 16) and is the most important preventive measure. Treatment consists of supportive care, with attention to maintaining good hydration.
▪ Rubella
Rubella is an RNA virus of the Togaviridae family (Chapter 391). Infection with this virus leads to an illness involving the skin, lymph nodes, and occasionally the joints, primarily in young children. The disease is spread by nasal droplet infection and has an incubation period of 14 to 21 days. Patients are most contagious when the rash is erupting. In children there may be no prodrome; in adults, however, fever, sore throat, and rhinitis may be present. The exanthem begins as pink macules and papules on the face that spread to the trunk and extremities; it lasts 1 to 3 days. Generalized tender lymphadenopathy, especially the suboccipital, postauricular, and cervical nodes, is the hallmark of rubella. In normal children and adolescents, the diagnosis is made clinically and laboratory work is unnecessary. If the diagnosis is questioned, a rising IgM antibody titer over a 2-week period indicates recent infection. No treatment exists, and the disease is usually self-limited. Rest and fluids are appropriate. The best protection is vaccination given with measles and mumps vaccine (i.e., MMR) at 12 to 15 months and again at 4 to 6 years (Chapter 16).
▪ Erythema Infectiosum
Erythema infectiosum is an exanthem caused by human parvovirus B19 (Chapter 394). It has a 4- to 14-day incubation period and is spread by aerosolized respiratory droplets. Acute infection leads to the production of IgM antibodies and the formation of immune complexes, which are deposited in the skin and joints. Bright red erythema appears abruptly over the cheeks. Within 1 to 4 days, an erythematous morbilliform eruption occurs on the extremities; it fades within several days to a reticulate pattern (Fig. 465-1). There may also be malar erythema or a reticulate eruption on the extremities. Exposure of adults to parvovirus B19 leads to an acute polyarthropathy of the hands, wrists, knees, and ankles. Parvovirus B19 can interfere with erythropoiesis (Chapter 171) and can cause aplastic crisis in patients with sickle cell disease (Chapter 167). The diagnosis is clinical, and further testing is not generally necessary. Erythema infectiosum is usually a benign, self-limited disease.
 |
| FIGURE 465-1 Reticulate macular erythema on the thigh of a patient with erythema infectiosum. |
▪ Roseola
Roseola (exanthem subitum) is caused by human herpesvirus 6 (Chapter 397). Virus replication occurs in leukocytes and salivary glands. Early invasion of the central nervous system (CNS) may lead to seizures. The classic patient is a healthy 9- to 12-month-old with an abrupt onset of high fever (40° C [104° F]) lasting for 3 days. Febrile seizures occur in 15% of cases. Its rapid defervescence is striking, with the onset of a generalized pink morbilliform exanthem. The eruption lasts 2 days and consists of pink papules or blanchable macular erythema. The lack of symptoms during the febrile phase and appearance of the exanthem as the fever subsides help with the diagnosis, but rubella and measles must also be considered. In an immunocompromised child or adult, there is usually an abrupt onset of fever, malaise, and sometimes CNS involvement. Virus isolation, seroconversion (IgM), or detection of viral DNA sequences in peripheral blood mononuclear cells can confirm the diagnosis. No antiviral therapy is available for roseola, and treatment is supportive. Practically all immunocompetent patients recover from roseola without sequelae, but chronic infection with multisystem complications may develop in immunocompromised patients.
▪Papular Eruptions
▪ Molluscum Contagiosum
Molluscum contagiosum is a cutaneous infection caused by a large DNA poxvirus that affects both children and adults. Firm, smooth, umbilicated papules, usually 2 to 6 mm in diameter, are present in groups or widely disseminated on the skin and mucosal surfaces. Patients infected with human immunodeficiency virus (HIV) may have hundreds of lesions, and some lesions can be larger than 15 mm (Chapter 415). The diagnosis is made on clinical grounds. Molluscum contagiosum is self-limited, with the goal of treatment being destruction of the lesions. Commonly used treatments are all topical and include cryotherapy with liquid nitrogen, curettage, cantharidin, podophyllin, and tretinoin.
▪ Warts
Warts are benign proliferations of skin and mucosa caused by human papillomaviruses (HPVs) (Chapter 396). More than 150 types of HPV have been identified. Certain types of HPV occur at particular anatomic sites; however, warts of any HPV type may be found at any site. Variants include common warts, genital warts, flat warts, and deep palmoplantar warts. Common warts, known as verruca vulgaris, are hard papules that range in size from 1 mm to more than 1 cm with a rough scaly surface (Fig. 465-2) and can occur anywhere on the body. Warts are transmitted by direct contact, and disruption of the epithelial barrier is a predisposing factor. HPV subtypes 6, 11, 16, 18, 31, and 35 may be associated with malignancies (Chapter 396). Malignant transformation, though uncommon, can occur in patients with genital warts or in immunocompromised patients. Infection is confined to the epithelium and does not result in systemic viral dissemination. The diagnosis is made on clinical grounds. Viral DNA identification via Southern blot hybridization is used to identify specific HPV subtypes. All therapies are methods of physical destruction of the skin where the virus is located because there are no specific antipapillomavirus medications. Common topical therapies include in-office treatment with liquid nitrogen, cantharidin, or podophyllin, as well as prescription-strength tretinoin or imiquimod. Over-the-counter liquid nitrogen is not as cold nor as effective as in-office treatment.
 |
| FIGURE 465-2 Hand of a patient with verruca vulgaris revealing many verrucous papules. |
▪Purpuric Eruptions
Purpura occurs when red blood cell extravasation leads to visible hemorrhage in the skin (Table 465-2). Petechiae (<3 mm) and purpura (>3 mm) may be nonpalpable or palpable. When the condition is severe, petechiae and purpuric lesions may become confluent and form ecchymoses larger than 1 cm.
Click here to view this table….
▪ Nonpalpable Purpura
▪Dermal Causes
Frequent causes of nonpalpable purpura include solar purpura, steroid purpura, and Schamberg's disease. Solar purpura, caused by chronic sun exposure and aging, is usually found on the forearms. Steroid purpura, which is due to prolonged use of topical or systemic steroids, can occur in any location (Chapter 33). Both conditions are caused by changes in the dermal connective tissue surrounding blood vessels. Schamberg's disease, or pigmented purpuric dermatosis, is a capillaritis with yellow-brown macules and petechiae on the lower part of the legs. This capillaritis occurs as a result of red blood cell extravasation secondary to perivascular lymphocyte inflammation.
▪Systemic Causes
Systemic causes of nonpalpable purpura include idiopathic thrombocytopenia purpura (Chapter 179), abnormal platelet function as a result of renal or hepatic insufficiency (Chapters 131 and 158) or thrombocytosis as seen in myeloproliferative diseases (Chapter 177), and clotting factor abnormalities (Chapter 181). Fragility of the blood vessels, especially the capillaries, is found in Ehlers-Danlos syndrome (Chapter 281), scurvy (Chapter 232), and systemic amyloidosis (Chapter 296).
▪Thrombi
Thrombus formation within skin blood vessels also leads to purpura in patients with disseminated intravascular coagulation (Chapter 181), thrombotic thrombocytopenia purpura (Chapter 179), monoclonal cryoglobulinemia (Chapter 198), and drug reactions to warfarin (Chapter 35). Disseminated intravascular coagulation may be caused by infectious agents (bacterial, particularly meningococcemia, viral, or rickettsial) and by malignancies such as leukemia (Chapter 181). Purpura fulminans is a type of disseminated intravascular coagulation associated with fever and hypotension; it is usually found in children after a bacterial or viral infection. Widespread purpura and hemorrhagic bullae can be seen in disseminated intravascular coagulation and purpura fulminans (Fig. 465-3). Thrombotic thrombocytopenia purpura (Chapter 179) is manifested as fever, purpura, renal failure, microangiopathic hemolytic anemia, and neurologic disease. Monoclonal cryoglobulinemia may be associated with leukemia, lymphoma, multiple myeloma, and Waldenström's macroglobulinemia. Mixed cryoglobulinemia is frequently associated with hepatitis C infection (Chapter 152). Widespread purpura along with ulcerations limited to the lower extremities or fingers and toes can occur. Skin biopsy specimens may reveal intracapillary deposits of precipitated cryoglobulins. Disease can be worsened by exposure to cold. The vessels of the lungs, brain, and kidneys may be involved. Warfarin necrosis of the skin (Chapter 35) is an uncommon reaction that occurs between the third and tenth day of therapy and is characterized by painful erythematous to purpuric plaques in which hemorrhagic bullae develop. The most common sites include the breasts, thighs, and buttocks. The onset of disease is unrelated to the dose of warfarin, and continued warfarin therapy does not alter the course of the disease.
 |
| FIGURE 465-3 Purpura fulminans. Purpura and hemorrhagic blisters are seen on the arm of this patient. |
▪Emboli
Cholesterol emboli are found in the lower extremities of patients with severe atherosclerosis as a result of occlusion of small- and medium-caliber arteries by cholesterol crystals (Chapter 126). Cholesterol emboli are triggered by vascular procedures or thrombolytic therapy, but they can also occur spontaneously. Other sources of emboli that may cause petechiae or purpura include fat emboli occurring after major injury (Chapters 99 and 113), tumor emboli from atrial myxomas (Chapter 59), emboli from infective endocarditis (Chapter 76), or nonbacterial thrombotic endocarditis (Chapters 59 and 189).
▪ Palpable Purpura
▪Vasculitis
Palpable purpura results from inflammatory damage to cutaneous blood vessels. Leukocytoclastic vasculitis, which is manifested as palpable purpura (Fig. 465-4), may be idiopathic or associated with sepsis, drug reactions, connective tissue diseases, cryoglobulinemia, hepatitis B or C infection, or underlying malignancies. Appropriate evaluation of patients with palpable purpura should always include histopathologic evaluation to confirm the diagnosis. Skin biopsy specimens from patients with leukocytoclastic vasculitis reveal angiocentric inflammation with endothelial cell swelling, fibrinoid necrosis of blood vessel walls, a neutrophilic cellular infiltrate with fragmentation of nuclei (karyorrhexis or leukocytoclasia) around and within blood vessel walls, and extravasated red blood cells (Fig. 465-5). Fresh skin biopsy specimens processed for direct immunofluorescence reveal deposits of immunoglobulins and complement in blood vessel walls. Once the diagnosis is confirmed, routine blood tests (including testing of renal and liver function) and urinalysis should be performed in all patients, whereas specialized tests should be targeted to specific patients with suggestive findings. If an etiologic agent can be identified and treated, the vasculitis will often resolve. Patients with idiopathic leukocytoclastic vasculitis can be treated with oral colchicine (0.6 mg twice daily), oral dapsone (100 mg once daily), or in the most severe cases, immunosuppressive agents such as azathioprine (up to 2.5 mg/kg for as long as the disease is active, as guided by the thiopurine methyltransferase level) or cyclophosphamide (up to 2 mg/kg for as long as the disease is active).
 |
| FIGURE 465-4 Palpable purpura. Leukocytoclastic vasculitis commonly causes raised purpuric and ulcerated lesions on the legs. |
 |
| FIGURE 465-5 Leukocytoclastic vasculitis. Histologic evaluation reveals a smudged blood vessel in the dermis with neutrophils, neutrophilic, dust, and red blood cells. |
Henoch-Schönlein purpura is a leukocytoclastic vasculitis that affects children and young adults; it is often preceded by an upper respiratory infection with associated fever, arthralgias, abdominal pain, and renal vasculitis (Chapter 179). Direct immunofluorescence reveals IgA deposits in dermal blood vessels.
Urticarial or hypocomplementemic vasculitis (Chapter 291) is characterized by urticarial lesions that last longer than 24 hours; arthritis, facial, and laryngeal edema; and low serum complement levels. In some patients, systemic lupus erythematosus (Chapter 287) may develop. In polyarteritis nodosa (Chapter 291), vasculitis of the arterial blood vessels leads to ischemia of the skin. Skin lesions usually include ulcerated nodules and ecchymoses.
▪Cutaneous Emboli
In addition to vasculitis, cutaneous emboli can also lead to the development of palpable purpura. Infectious emboli (Chapter 76) can be caused by gram-negative cocci, gram-negative rods, Rickettsia, and in immunocompromised patients, Candida and opportunistic fungi. Acute meningococcemia (Chapter 311) occurs after an upper respiratory tract infection and is associated with headache, fever, meningitis, hypotension, and disseminated intravascular coagulation. The embolic lesions, which are found on the trunk and lower extremities, can range from 1 mm up to several centimeters. Disseminated gonococcal infection (Chapter 322) is accompanied by fever, arthralgias, tenosynovitis, and a small number of vesiculopustules with purpura or hemorrhagic necrosis over the distal ends of the extremities. Rocky Mountain spotted fever (Chapter 348) is a tick-borne disease characterized by headache, fever, chills, photophobia, and myalgias. The cutaneous eruption starts acrally and spreads centripetally as small, erythematous, blanchable macules that evolve into petechiae, palpable purpura, and ecchymoses. Ecthyma gangrenosum is manifested as erythematous papules and plaques in which central purpura and hemorrhagic necrosis develop; Pseudomonas aeruginosa (Chapter 328) is the most common organism, but Klebsiella (Chapter 309), Escherichia coli (Chapter 327), and Serratia (Chapter 309) have also been implicated. In immunocompromised patients, ecthyma gangrenosum may develop as a result of infection with Candida or opportunistic fungi.
▪VESICULOBULLOUS DISEASES
Vesicles are clear, fluid-filled lesions measuring less than 5 mm; bullae or blisters are clear, fluid-filled lesions larger than 5 mm. Vesiculobullous lesions in the skin may be caused by immunologically mediated mechanisms, hypersensitivity reactions, metabolic disorders, inherited genetic defects, and infections (Table 465-3).
Click here to view this table….
▪Immunologically Mediated Blistering Diseases
▪ Bullous Pemphigoid
Definition
Bullous pemphigoid is an autoimmune blistering disease of the elderly. Tense blisters and urticarial plaques occur on the flexor surfaces of the arms and legs, axilla, groin, and abdomen (Fig. 465-6).
 |
| FIGURE 465-6 Bullous pemphigoid. Tense subepidermal bullae are seen on an erythematous base. |
Pathobiology
IgG autoantibodies bind to the epidermal basement membrane and activate complement, which attracts inflammatory cells. These inflammatory cells release proteases that degrade basement membrane proteins and lead to blister formation. Histology reveals a subepidermal blister with an eosinophilic infiltrate. Direct immunofluorescence shows linear deposits of IgG and C3 at the basement membrane. Indirect immunofluorescence studies using salt-split skin demonstrate circulating IgG antibodies that bind to the epidermal side.
Treatment
Treatment is dictated by the degree of involvement and the rate of progression of the disease. A randomized, multicenter trial demonstrated that 40 g of the ultrapotent topical steroid clobetasol, applied twice daily to the skin of patients with bullous pemphigoid until 15 days after disease control was obtained, was effective and superior to oral corticosteroid treatment in patients with both moderate and severe disease.1 Nevertheless, the practicality of such potent topical steroids is controversial, and many experts use oral prednisone, 1 mg/kg in an early morning daily dose, as a foundation of therapy for patients with generalized bullous pemphigoid. Other treatments include tetracycline (500 mg four times daily), dapsone (up to 150 mg daily), azathioprine (up to 2.5 mg/kg as guided by the thiopurine methyltransferase level), methotrexate (up to 15 mg weekly), mycophenolate mofetil (35 to 45 mg/kg divided into two daily doses), and cyclophosphamide (up to about 2 mg/kg). The duration of therapy with all of these medications varies, depending on the activity of the disease. Left untreated, bullous pemphigoid generally persists for months to years. Spontaneous remissions and exacerbations occur. The mortality rate is relatively low, even without treatment.
▪ Herpes Gestationis
Herpes gestationis is a rare autoimmune dermatosis of pregnancy. Despite the name, herpes gestationis has no relationship to herpesvirus infection. Most patients have intense pruritus. Periumbilical urticarial plaques progress to vesicles and blisters. The eruption spreads peripherally (Fig. 465-7), typically sparing the face, palms, soles, and mucous membranes. IgG autoantibodies are produced against bullous pemphigoid antigen II, which is critical in epidermal-dermal adhesion. Antibody binding triggers an immune response leading to blister formation. Histology reveals a subepidermal blister, and direct immunofluorescence shows linear C3 deposits at the basement membrane.
 |
| FIGURE 465-7 Herpes gestationis. Multiple tense blisters and erosions on an erythematous base are present. |
Corticosteroids are the mainstay of therapy. Patients with mild disease are treated with moderate- to high-potency topical corticosteroids, such as 0.05% fluocinonide ointment applied twice daily to affected areas, whereas patients with extensive disease usually require systemic corticosteroids, such as prednisone, 1 mg/kg given once daily as an early morning dose. Disease clears within 1 to 2 weeks after initiation of treatment. There is an increased risk for premature delivery and birth of infants who are small for gestational age, thus suggesting that these women should be managed by obstetricians experienced in high-risk pregnancies.
▪ Mucous Membrane Pemphigoid
Definition
Mucous membrane pemphigoid, previously called cicatricial pemphigoid, is a group of subepithelial blistering diseases that involve the mucosal surfaces. Patients have blisters of the oral, ocular, nasopharyngeal, laryngeal, anogenital, and esophageal mucosa that heal with scarring, which causes the major morbidity associated with the disease.
Pathobiology
There are several subgroups of mucous membrane pemphigoid. Some patients have circulating IgG autoantibodies that bind to the dermal side of salt-split skin and recognize laminin 5. A second subgroup includes patients who have pure ocular disease and IgG antibodies directed against β4 integrin. A third subgroup has mucosal disease and skin lesions. The fourth variant includes patients with oral disease but without skin disease. Histology reveals a subepidermal blister with an inflammatory cell infiltrate. Direct immunofluorescence shows linear IgG, IgA, and C3 deposits at the basement membrane. Indirect immunofluorescence reveals circulating IgG or IgA antibodies, or both.
Treatment
Treatment is dictated by the extent, severity, and location of disease; it ranges from topical corticosteroids, such as 0.05% fluocinonide ointment applied twice daily to affected areas under occlusion in patients with only oral disease, to prednisone, 1 mg/kg given once daily as an early morning dose, and cyclophosphamide, up to 2 mg/kg given as an early morning dose for up to 2 years, for severe ocular disease. Management teams should include ophthalmologists, otolaryngologists, dermatologists, and internists for patients with severe disease. Patients with both circulating IgG and IgA antibodies tend to have more severe disease.
Prognosis
Mucous membrane pemphigoid is a chronic disease. Untreated ocular disease can result in blindness.
▪ Epidermolysis Bullosa Acquisita
Epidermolysis bullosa acquisita is an acquired autoimmune blistering disease that generally occurs in middle age. There are two types of skin lesions: noninflammatory acral blisters that heal with scarring and milia formation and widespread inflammatory vesiculobullous disease.
Pathobiology
Epidermolysis bullosa acquisita is characterized by IgG autoantibodies that target collagen VII, the major protein of anchoring fibrils. These autoantibodies alter dermal-epidermal adhesion and lead to blister formation. Histology reveals a subepidermal blister containing few inflammatory cells when mechanobullous lesions are sampled or a neutrophil-rich infiltrate when inflammatory blisters are sampled. Direct immunofluorescence reveals linear IgG deposits at the basement membrane. Indirect immunofluorescence shows circulating IgG autoantibodies that bind the dermal side of salt-split skin.
Treatment
Epidermolysis bullosa acquisita is a chronic disease that is very difficult to treat. Dapsone (at doses up to 150 mg daily), colchicine (0.6 mg twice daily), azathioprine (up to 2.5 mg/kg as guided by the thiopurine methyltransferase level), or cyclophosphamide (2 mg/kg given as an early morning dosage) alone or along with prednisone (60 mg given once daily as an early morning dose) is only occasionally successful. Cyclosporine at doses of up to 5 mg/kg or extracorporeal photopheresis has been used successfully in patients with severe disease. Because of nephrotoxicity, cyclosporine should be reserved for crisis management of patients who have severe disease and are experiencing a major flare.
▪ Dermatitis Herpetiformis
Dermatitis herpetiformis is an immune-mediated vesicular disease that usually occurs in the young to middle aged. Skin lesions are extremely pruritic grouped vesicles and erosions located on the scalp, posterior of the neck, and extensor surfaces of the elbows, knees, and buttocks (Fig. 465-8). Most patients have a subclinical gluten-sensitive enteropathy (Chapter 143) that is reversible with a gluten-free diet. Diet alone can sometimes control the skin disease, with clearance of the cutaneous granular IgA deposits at the basement membrane. Biopsy specimens of skin lesions reveal dermal papillary neutrophilic microabscesses. Direct immunofluorescence shows dermal papillary granular IgA deposits in all patients. Dermatitis herpetiformis can be treated with dapsone, usually 100 mg daily given chronically. Dermatitis herpetiformis is a lifelong disease.
 |
| FIGURE 465-8 Dermatitis herpetiformis. The elbow of a patient has eroded erythematous papules and papulovesicles. |
▪ Linear IgA Bullous Dermatosis
Linear IgA bullous dermatosis is an acquired autoimmune blistering disease of the skin. The primary lesions are papulovesicles, and involvement of the oral mucous membranes is common. The disease occurs throughout adulthood. Deposition of IgA antibody specific for a portion of bullous pemphigoid antigen II leads to complement activation and neutrophil chemotaxis. Proteolytic enzymes are released, destroy the dermal-epidermal junction, and cause blister formation. Histology reveals a subepidermal vesicle or cleft with neutrophil predominance. Direct immunofluorescence shows linear deposits of IgA at the basement membrane. Indirect immunofluorescence demonstrates circulating IgA antibodies. The majority of patients respond to dapsone, 100 mg daily, given chronically. Patients whose disease is not controlled with dapsone may benefit from the addition of oral prednisone, 1 mg/kg once daily as an early morning dose. The disease tends to be chronic in adults, but the childhood version (called chronic bullous disease of childhood) may run a several-year course and then remit.
▪ Pemphigus
Definition
Pemphigus refers to a group of autoimmune blistering intraepidermal diseases of the skin and mucous membranes that are most common in middle age.
Clinical Manifestations
Patients with pemphigus vulgaris have flaccid blisters and erosions in the oropharynx (Fig. 465-9), trunk, head, neck, and intertriginous areas. Pemphigus foliaceus is accompanied by erythema, scaling, and crusting of the face, scalp, and upper part of the trunk. Patients with paraneoplastic pemphigus have ocular and oral blisters and erosions along with skin lesions resembling erythema multiforme and an associated underlying malignancy that is generally lymphoreticular in origin (Chapter 189).
 |
| FIGURE 465-9 Pemphigus vulgaris. The lower lip of a patient has confluent erosions with scattered crusting. |
Pathobiology
Autoantibodies in pemphigus vulgaris target desmoglein III, and autoantibodies in pemphigus foliaceus target desmoglein I. Circulating antibodies in paraneoplastic pemphigus recognize a complex of proteins, including desmoplakin I and II, bullous pemphigoid antigen I, envoplakin, periplakin, and desmoglein I and III.
Diagnosis
Skin biopsy specimens from patients with pemphigus vulgaris reveal suprabasilar acantholysis, whereas pemphigus foliaceus biopsy specimens demonstrate subcorneal acantholysis. Biopsy specimens of paraneoplastic pemphigus show suprabasilar acantholysis and dyskeratotic keratinocytes with basal cell vacuolization.
Direct immunofluorescence demonstrates cell surface deposits of IgG in patients with pemphigus vulgaris and foliaceus, whereas indirect immunofluorescence reveals circulating IgG antibodies. Patients with paraneoplastic pemphigus have circulating and tissue-bound IgG antibodies that are indistinguishable from those in pemphigus vulgaris and that also recognize the cell surface of simple epithelia, including the liver and heart.
Treatment
Treatment regimens depend on the patient's age, the degree of involvement, the rate of disease progression, and the subtype of pemphigus. Systemic corticosteroids (e.g., oral prednisone, 1 mg/kg once daily as an early morning dose) are required for pemphigus vulgaris, whereas topical corticosteroids (e.g., 0.05% fluocinonide ointment applied twice daily to affected areas) occasionally control pemphigus foliaceus. Steroid-sparing agents include dapsone (up to 150 mg daily), the combination of tetracycline (500 mg four times daily) and niacinamide (500 mg three times daily), hydroxychloroquine (administered at less than 6 mg/kg of lean body mass divided into two daily doses), mycophenolate mofetil (35 to 45 mg/kg/day divided into two daily doses), azathioprine (up to 2.5 mg/kg as guided by the thiopurine methyltransferase level), and cyclophosphamide (up to 2 mg/kg given as an early morning dose). The duration of therapy with each of these medications varies according to the level of disease activity. Although the use of steroid-sparing agents is supported by clinical experience, few controlled studies have demonstrated their benefit. For paraneoplastic pemphigus caused by benign tumors such as Castleman's disease (Chapter 196), tumor removal is curative. Patients with associated malignant tumors have recalcitrant disease, although there are occasional successes with pulse corticosteroids (methylprednisolone, 1000 mg given daily for 3 consecutive days), pulse cyclophosphamide (500 to 1000 mg given monthly for 6 months to 1 year, often along with varying doses of prednisone), immunoapheresis, and immunoablative high-dose cyclophosphamide (50 mg/kg/day for 4 days).
Prognosis
Before the availability of corticosteroids, 60 to 90% of patients with pemphigus vulgaris died, whereas the mortality rate has now decreased to the 5 to 10% range. The prognosis of patients with paraneoplastic pemphigus is related to the type of associated neoplasm. Patients with benign tumors usually experience clearance of their lesions after tumor resection, whereas those with malignant tumors generally have a poor prognosis.
▪Hypersensitivity Reactions That Cause Blisters
▪ Erythema Multiforme
Definition
Erythema multiforme is an acute blistering eruption that occurs in all age groups. Erythema multiforme minor is localized, with minimal or no mucosal involvement. Erythema multiforme major, also known as Stevens-Johnson syndrome, is a more severe mucosal and skin disease characterized by signs and symptoms reminiscent of serum sickness (Chapter 44).
Clinical Manifestations
Toxic epidermal necrolysis is at the most severe end of the erythema multiforme spectrum. The primary lesions of erythema multiforme minor are erythematous macules and edematous papules with vesicular centers that become dusky violet. Target or iris lesions are found on extensor surfaces of the extremities and spread centripetally (Fig. 465-10). The skin lesions of Stevens-Johnson syndrome resemble those of erythema multiforme minor but are likely to be generalized and show confluent erythema with urticarial and purpuric lesions. Erosions of two or more mucosal surfaces occur in Stevens-Johnson syndrome and may include hemorrhagic crusting of the lips, ulceration of the ocular mucosa, and genital involvement. Patients with erythema multiforme major have a 1- to 14-day prodrome that includes fever, cough, sore throat, vomiting, and diarrhea. Patients with toxic epidermal necrolysis may have a similar prodrome, rapidly followed by generalized macular erythema that progresses to confluent erythema with skin tenderness. Large blisters follow soon afterward, and then skin sloughing occurs as the large blisters break and leave denuded skin.
 |
| FIGURE 465-10 Erythema multiforme. Target or “bull's-eye” annular lesions with central vesicles and bullae are characteristic of erythema multiforme. |
Pathobiology
Common etiologic associations of erythema multiforme include infections such as herpes simplex (Chapter 397) (especially recurrent erythema multiforme minor), Mycoplasma pneumoniae (Chapter 338), and drug reactions (Chapter 275). Sulfonamides, penicillins, barbiturates, carbamazepine, phenytoin, allopurinol, and nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common drugs implicated in Stevens-Johnson syndrome and toxic epidermal necrolysis.
Diagnosis
The diagnosis of erythema multiforme is clinical.
Treatment
Chronic antiviral treatment with acyclovir (400 mg twice daily for 6 months) decreases outbreaks in a subset of patients with recurrent erythema multiforme minor. Treatment of erythema multiforme major is otherwise nonspecific, with attention to fluid and electrolyte balance and eye disease being critical. If a drug is suspected, it must be withdrawn. Systemic corticosteroid treatment is contraindicated in Stevens-Johnson syndrome. Treatment of toxic epidermal necrolysis is very difficult, but uncontrolled studies suggest that intravenous immunoglobulin (2 to 3 g/kg over a period of 2 to 5 days) may improve the prognosis.
Prognosis
Erythema multiforme minor usually subsides within 2 to 3 weeks. Erythema multiforme major takes 3 to 6 weeks to clear and has less than a 5% mortality rate. Toxic epidermal necrolysis has a mortality rate approaching 30%, and patients are best managed in an intensive care or burn unit.
▪Metabolic Disorders That Cause Blisters
▪ Porphyria Cutanea Tarda
Porphyria cutanea tarda is caused by deficient activity of the heme synthetic enzyme uroporphyrinogen decarboxylase (Chapter 229). The fragility of sun-exposed skin leads to erosions and bullae, which are worst on the dorsal surface of the hands (Fig. 465-11), forearms, and face. Healing of crusted erosions and blisters leaves scars, milia, and hyperpigmented and hypopigmented atrophic patches. Hypertrichosis is common and most florid over the temporal and malar areas. Urinary porphyrin levels are abnormally high. Histology reveals a subepidermal blister with minimal dermal infiltrate, and direct immunofluorescence demonstrates immunoglobulin and complement deposition in dermal capillaries and at the basement membrane. Phlebotomy is the standard treatment, and the goal is to reduce serum ferritin to the lower limit of the normal range. Another treatment option is oral hydroxychloroquine at a dose (200 mg twice weekly until the disease is under control) that is much lower than that used for photoprotective indications. Alcohol and estrogen use should be discontinued because they can cause the disease to flare.
 |
| FIGURE 465-11 Porphyria cutanea tarda. A blister and erosions are present on the dorsal surface of the hand. |
▪ Pseudoporphyria
Pseudoporphyria is a bullous eruption that mimics porphyria cutanea tarda clinically and histologically without porphyrin abnormalities. Many medications can cause pseudoporphyria, including propionic acid–derivative NSAIDs (e.g., naproxen, diflunisal, ketoprofen, nabumetone, oxaprozin, and mefenamic acid), furosemide, tetracycline, fluoroquinolones, amiodarone, cyclosporine, dapsone, etretinate, and flutamide. The prognosis is good for patients with pseudoporphyria after the offending agent has been discontinued. However, resolution of the disease may take several months. In patients with chronic renal failure treated by hemodialysis, true porphyria cutanea tarda or pseudoporphyria may develop and is very difficult to treat.
▪ Diabetes Mellitus
Distal extremity blisters may occasionally develop in patients with diabetes mellitus (Chapter 247). There is no correlation between the development of blisters and the severity, duration, or complications of diabetes. The mechanism of blister formation is not understood.
▪Inherited Genetic Disorders That Cause Blisters
Epidermolysis bullosa is a group of inherited bullous disorders characterized by blister formation in response to mechanical trauma. Subtypes include epidermolysis bullosa simplex (intraepidermal skin separation) (Fig. 465-12), junctional epidermolysis bullosa (skin separation in the lamina lucida), and dystrophic epidermolysis bullosa (sublamina densa separation). Infancy is an especially difficult time, and epidermolysis bullosa may be accompanied by blistering that is complicated by infection and sepsis. Many patients with junctional epidermolysis bullosa have severe disease that can lead to death, usually secondary to infection, and metastatic squamous cell carcinoma may develop in some patients with recessive dystrophic epidermolysis bullosa and can also lead to death. In contrast, epidermolysis bullosa simplex, milder forms of junctional epidermolysis bullosa, and dominant dystrophic epidermolysis bullosa do not usually affect life expectancy. Epidermolysis bullosa simplex is caused by mutations of the genes coding for keratins 5 and 14. Junctional epidermolysis bullosa has a variable molecular etiology, and mutations in genes coding for laminin 5 subunits, bullous pemphigoid antigen I, α6 integrin, and β4 integrin have been demonstrated. Dystrophic epidermolysis bullosa is caused by mutations of the type VII collagen gene. Epidermolysis bullosa is a lifelong disease. Some subtypes, especially the milder forms, improve with age. No medications are known to correct the underlying molecular defects, but gene therapy is being actively pursued.
 |
| FIGURE 465-12 Epidermolysis bullosa simplex. Tense blisters and erosions are present on the trunk and extremities of a newborn. |
▪Infectious Diseases That Cause Blisters
▪ Impetigo
Impetigo is a bacterial infection of the superficial layers of the epidermis. Bullous impetigo is caused by S. aureus (Chapter 310), and nonbullous impetigo is caused by group A β-hemolytic streptococci (Chapter 312). Bullous impetigo is manifested as vesicles and bulla (Fig. 465-13). Lesions are common on the face but may appear anywhere. Nonbullous impetigo is characterized by fragile vesicles or pustules that rupture and leave honey-colored crusted papules or plaques, especially near the nose and mouth and on the extremities. Lesions develop on normal or traumatized skin or are superimposed on preexisting conditions, including scabies, varicella, or atopic dermatitis. The causative agent of bullous impetigo is coagulase-positive S. aureus, which produces exfoliatins A and B. The toxins cause cleavage within or below the stratum granulosum. Impetigo is diagnosed clinically. Culture and sensitivity studies are recommended if topical or oral treatment is ineffective. Oral antibiotics, including dicloxacillin (500 mg four times daily for 7 days) or cephalexin (500 mg three times daily for 7 days), applied twice daily for 7 days, are used for extensive disease or in patients refractory to topical mupirocin. Gentle débridement of crusts is recommended. Lesions resolve after 7 to 10 days of treatment. Acute glomerulonephritis (Chapter 122) develops in 2 to 5% of young children with nonbullous impetigo, usually within 10 days after the skin lesions appear.
 |
| FIGURE 465-13 Bullous impetigo. Multiple blisters are present on the trunk of this patient. |
▪ Staphylococcal Scalded Skin Syndrome
Staphylococcal scalded skin syndrome is a blistering disease caused by an exotoxin produced by S. aureus (Chapter 310). It is most common in young children but may occur in adults who have renal insufficiency or are immunocompromised. The site of the staphylococcal infection is usually extracutaneous. Staphylococcal scalded skin syndrome is manifested as a sudden onset of fever and tender, blanchable erythema. It starts on the central part of the face, neck, and intertriginous areas and rapidly generalizes. The palms, soles, and mucous membranes are spared. Flaccid blisters occur within 1 to 2 days and soon exfoliate in large sheets, with superficially denuded skin remaining (Fig. 465-14). The disease must be distinguished from toxic epidermal necrolysis by skin biopsy. In staphylococcal scalded skin syndrome there is an upper epidermal blister, whereas toxic epidermal necrolysis causes a dermal-epidermal blister. Patients with the most severe staphylococcal scalded skin syndrome should be treated with intravenous nafcillin or oxacillin, 2 g every 4 to 6 hours for 10 to 14 days. If the patient is found to have methicillin-resistant staphylococci, vancomycin, 1 g every 12 hours (with dose adjustment based on creatinine clearance), should be given for 10 to 14 days. Patients with mild disease may be treated with oral dicloxacillin, 500 mg four times daily for 10 to 14 days, unless the staphylococcal isolate is methicillin resistant, in which case the choice of antibiotics should be guided by the results of sensitivity testing.
 |
| FIGURE 465-14 Staphylococcal scalded skin syndrome. Confluent erythema with exfoliation of skin is seen on the trunk. |
▪ Herpes Simplex Virus Infection
Pathobiology
Herpes simplex virus (HSV) infection (Chapter 397) may be caused by type 1 or type 2 HSV. The hallmark of HSV infection is its ability to establish latent infection. Disease commonly occurs as a recurrent vesicular eruption of the oral, perioral (typically HSV-1), or genital (typically HSV-2) regions, although primary gingivostomatitis (typically in children and young adults and caused by HSV-1) and primary genital herpes (typically HSV-2) are less common.
Clinical Manifestations
Patients with primary gingivostomatitis have high fever, regional lymphadenopathy, and malaise. Patients with primary genital herpes have fever, flulike symptoms, tender inguinal adenopathy, and aseptic meningitis. These infections all reveal grouped vesicles on an erythematous base. Recurrent eruptions can be triggered by skin trauma, cold or heat, concurrent infection, and menstruation. Chronic erosive ulcers of the face and anogenital areas may develop in immunocompromised patients.
Diagnosis
Tzanck smear of fluid from the roof of a vesicle can be helpful in confirming the diagnosis (see Fig. 462-15), but viral culture is the diagnostic “gold standard.” The direct fluorescent antibody test is an antigen-based technique that not only yields same-day results but can also distinguish HSV from varicella-zoster virus (VZV) and is becoming widely used.
Treatment
In healthy individuals, HSV infection is self-limited. The goal of treatment is to shorten the current attack and prevent recurrences. Acyclovir is effective in the treatment of HSV infections; valacyclovir and famciclovir are closely related, effective medications with improved oral bioavailability. The doses and duration of therapy vary depending on whether the infection is limited to the oral or genital mucous membranes or is disseminated and on whether it is primary or recurrent disease (Chapter 397).
▪ Chickenpox
Chickenpox is caused by VZV (Chapter 398). It is usually a childhood disease, but affected adults have more morbidity. Skin lesions occur 10 to 21 days after exposure to VZV. Erythematous macules appear on the scalp, face, trunk, and proximal ends of the limbs, with rapid progression to papules, vesicles, pustules, and crusting (Fig. 465-15). Adults may experience a more widespread eruption, prolonged fever, and pneumonia. The diagnosis is usually made clinically, but direct fluorescent antibody or culture confirmation is sometimes needed. Treatment of healthy children is unnecessary because the disease is self-limited. Adults should be treated with oral acyclovir, 800 mg five times a day for 7 days. The varicella vaccine given once to healthy children 12 to 18 months of age and twice, in a 4- to 8-week interval, to susceptible persons older than 13 years (Chapter 16) is highly effective.
 |
| FIGURE 465-15 Erythematous macules and vesicles with crusted erosions on the chest of a patient with varicella. |
▪ Herpes Zoster
Pathobiology
Herpes zoster is caused by reactivation of VZV from a previous chickenpox infection. The disease is more common in older or immunocompromised patients.
Clinical Manifestations
The typical manifestation is painful grouped herpetiform vesicles on an erythematous base confined to cutaneous surfaces innervated by one sensory nerve and preceded by radicular pain (Fig. 465-16). The major morbidity, which is pain within the affected dermatome, can be severe and persist after the skin lesions have resolved (postherpetic neuralgia). Immunocompromised patients have an increased risk for cutaneous dissemination and visceral involvement of the bladder, lungs, and CNS.
 |
| FIGURE 465-16 Herpes zoster. Necrotic blisters and erosions in a dermatomal pattern are seen on the trunk of this patient. |
Treatment
Acyclovir (800 mg orally five times daily for 7 days) and its derivatives valacyclovir (500 mg orally three times daily for 7 days) and famciclovir (500 mg orally three times daily for 7 days) are safe and effective in the treatment of active disease and prevention of postherpetic neuralgia. In an immunocompromised patient, acyclovir should be given intravenously (10 mg/kg every 8 hours for 7 to 10 days). The earlier antiviral medications are started, the more effective they are in shortening the duration of herpes zoster and in preventing or decreasing the severity of postherpetic neuralgia. Although older uncontrolled studies suggested that 3 weeks of oral prednisone may decrease the incidence of both acute pain and postherpetic neuralgia, more recent controlled studies have failed to demonstrate any beneficial effects of systemic corticosteroids. Patients with postherpetic neuralgia of more than 3 months' duration benefit from the use of gabapentin, 1600 or 2400 mg daily, with a significant reduction in pain.2 VZV vaccine markedly reduces both the morbidity from herpes zoster and postherpetic neuralgia in healthy adults older than 60 years.3
▪PUSTULAR ERUPTIONS
▪Acne Vulgaris
Definition
Acne vulgaris is the most common pustular skin condition. Teenagers are usually affected, but the disease may persist into adulthood. The comedo, which is the primary lesion, can be either closed (whitehead) or open (blackhead).
Pathobiology
Androgen production after puberty stimulates the release of sebum by sebaceous glands. Sebum flow is impeded because of abnormal keratinization within the pilosebaceous canal, a process that leads to the formation of comedones. Bacterial (Propionibacterium acnes) proliferation within the comedo predisposes to rupture of the pilosebaceous unit with extravasation into the surrounding dermis, which results in papules, pustules, and cysts.
Treatment
Patients with mild disease are treated topically with benzoyl peroxide, tretinoin, adapalene, or tazarotene, which normalize follicular keratinization. In patients with mild to moderate disease, treatment with benzoyl peroxide is the most cost-effective therapy.4 The addition of topical antibiotics helps control inflammatory papules and pustules. More significant disease is often treated with oral tetracycline (250 to 1000 mg/day), doxycycline (200 mg/day), or minocycline (200 mg/day). Dapsone gel (5%) is safe and effective.5 Another approach is oral contraceptives containing ethinyl estradiol and norgestimate, which are superior to placebo in the treatment of acne in women. Isotretinoin (Accutane) (1 mg/kg given for 5 months), which decreases sebaceous gland size and sebum production, is reserved for severe cystic disease because of its teratogenicity, possible associated risk for depression, and other significant side effects. Acne may be exacerbated by the use of oil-based cosmetics or hair preparations. Androgenic hormones, systemic corticosteroids, lithium, phenytoin, phenobarbital, isoniazid, and endocrinologic conditions such as polycystic ovary disease and adrenal or ovarian tumors may produce acneiform eruptions or aggravate preexisting acne.
▪ Rosacea
Rosacea, which is a chronic inflammatory disease of the face, affects the pilosebaceous units and blood vessels and generally occurs in middle age. Erythema, telangiectases, erythematous papules, and pustules occur on the central part of the face. Ocular rosacea can lead to keratitis, iritis, blepharitis, and recurrent chalazion; it should be managed by an ophthalmologist. In its most severe form, rosacea can cause sebaceous gland hyperplasia leading to a large red bulbous nose known as rhinophyma (Fig. 465-17). Rosacea is more likely to develop in patients with a tendency toward facial flushing. Flushing can be due to heat, spicy foods, hot drinks, alcohol, or emotional stimuli. With time, the flushing reaction lasts longer and longer until it persists. Topical antibiotics, including 1% metronidazole, are helpful in mild disease. Patients with more severe disease require oral tetracycline, 500 mg twice daily for 3 to 4 months and then slowly decreased as tolerated. Azelaic acid gel (15%) can significantly improve papulopustular rosacea.6
 |
| FIGURE 465-17 Sebaceous gland hyperplasia. A large red bulbous nose known as rhinophyma is characteristic of late-stage rosacea. |
▪ Perioral Dermatitis
Perioral dermatitis is characterized by erythematous papules and pustules, as well as scaling patches around the mouth and eyes (Fig. 465-18). Most patients have used potent topical corticosteroids inappropriately for long periods. The eruption generally clears after stopping the corticosteroid and using tetracycline, 250 mg orally twice daily for 6 weeks.
 |
| FIGURE 465-18 Perioral dermatitis. Erythematous papules and pinpoint pustules are evident around the mouth. |
▪ Acute Exanthematous Pustulosis
Acute exanthematous pustulosis is a generalized pustular eruption that is associated with fever and frequently caused by antibiotics. Pustules develop within 2 days of drug administration, start on the face or in flexural areas, and rapidly disseminate (Fig. 465-19). Spontaneous resolution occurs in less than 2 weeks.
 |
| FIGURE 465-19 Acute generalized exanthematous pustulosis. Erythematous macules and numerous superficial pustules are present on the trunk of this patient. |
▪ Pustular Psoriasis
Pustular psoriasis is a variant of psoriasis (Chapter 464) that localizes to the palms and soles or generalizes over the entire body. Patients with generalized disease have fever and leukocytosis and require systemic therapy. Pustules can also be seen in patients with septic emboli of bacterial or fungal origin, including gonococcemia and systemic candidiasis (see Purpuric Eruptions).
▪ Folliculitis
Folliculitis is inflammation of the hair follicles caused by infection with staphylococci. It is due to obstruction of individual hair follicles and associated pilosebaceous units. Folliculitis is more common in patients with diabetes mellitus, obesity, or immunocompromised states. The primary lesion is a pustule with a central hair. Typical affected sites are the scalp, thighs, trunk, axilla, and inguinal area. Sometimes the infection can extend deeper into the dermis and form larger erythematous nodules from one (furuncle) or more (carbuncle) follicles. Treatment with oral antibiotics such as cephalexin, 500 mg twice daily for 14 days, clears extensive infections, whereas topical antibiotics (e.g., clindamycin solution applied twice daily for 2 weeks or longer) and antibacterial soaps (e.g., Dial or Lever 2000) help in milder disease.
▪Pseudomonas Folliculitis
Pseudomonas folliculitis is acquired from hot tubs contaminated with Pseudomonas aeruginosa (Chapter 328). The typical finding is papules and pustules in areas of skin occluded by a bathing suit (Fig. 465-20). Treatment with ciprofloxacin at 500 mg twice daily for 10 to 14 days is usually curative.
 |
| FIGURE 465-20 Pseudomonas folliculitis. The trunk of this patient has numerous pustules on an erythematous base. |
Pityrosporum folliculitis is a pruritic, acne-like eruption that occurs on the upper part of the back and the chest, arms, and face and is caused by Pityrosporum ovale. Treatment is with oral ketoconazole, 200 mg/day for 2 weeks, and 2% ketoconazole shampoo applied to the affected area daily for 1 month.
▪Eosinophilic Pustular Folliculitis
Eosinophilic pustular folliculitis is a sterile, intensely pruritic folliculitis usually found on the face, chest, and back of patients who are positive for HIV (Chapter 415). Skin biopsy is needed to confirm the diagnosis. Treatment is difficult, but options include potent topical corticosteroids, such as 0.1% triamcinolone ointment applied twice daily for several months (although this class 4 steroid should not be used on the face); antihistamines, such as hydroxyzine, 25 mg every 8 hours as needed; and ultraviolet light therapy.
|
|