Meningococcemia and Purpura Fulminans

29 Meningococcemia and Purpura Fulminans Meningococcemia ᭿ Synonyms: Waterhouse-Friderichsen syndrome (with purpura fulminans and adrenal hemorrhage) ᭿ Etiology: Invasive infection with Neisseria meningitidis ᭿ Associations: Inherited or acquired deficiencies of complement or immunoglobulin in some cases ᭿ Clinical: Upper respiratory tract symptoms, then fever, myalgias, arthralgias; cutaneous involvement—macules, papules, petechiae, palpable purpura; purpuric necrotic patches of purpura fulminans ᭿ Histology: Skin biopsy with mixed lymphocyte and neutrophil infiltrate, ±vasculitis, organism may be found by Gram’s stain ᭿ Evaluation: Blood cultures, CBC with differential, platelets, PT/PTT, other coagulation parameters, Gram’s stain of smears from purpuric lesions ᭿ Treatment: Intravenous antibiotics—penicillin G or third generation cephalosporin, fluid and inotropic support; ±activated protein C infusion or bactericidal permeability increasing protein for severe sepsis ᭿ Prognosis: Good if treated early, but guarded with signs of sepsis or purpura fulminans Purpura Fulminans ᭿ Synonyms: Symmetrical peripheral gangrene ᭿ Etiology: Diffuse intravascular coagulation ᭿ Associations: Inherited protein C or S deficiency, postinfectious, bacteremic sepsis ᭿ Clinical: Widespread purpura with necrosis, skin and other organ systems ᭿ Evaluation: PT/PTT, protein C and S, antithrombin III, CBC with differential, platelets, fibrinogen, fibrin degradation products ᭿ Treatment: Reversal of underlying process ᭿ Prognosis: High incidence of long-term deformity related to necrosis and amputations, high mortality in that associated with sepsis. Meningococcemia is an invasive bacterial infection by the infants six months to one year, with a steady decline in gram-negative diplococcus, Neisseria meningitidis, which infection rate with age. This is likely explained by passive is often rapidly fatal if not detected and treated early. Neis- maternal immunity providing protection in the first six seria meningitidis infections occur both endemically and months, and gradual onset of acquired immunity with epidemically. Sporadic disease occurs more commonly age. Approximately two-thirds of invasive meningococcal during winter and early spring months, and affects pre- disease occurs in children (1). The human bacterial reser- dominantly children. The highest rate of infection is in voir is the upper respiratory tract. In the general popula- 137 138 Deadly Dermatologic Diseases tion, the carrier state is quite common, but in only rare complement as may occur in chronic liver disease, sys- cases do carriers develop invasive disease. There are many temic lupus erythematosus, and multiple myeloma also different serotypes of Neisseria meningitidis, but types A, predispose to invasive meningococcal infection (4,8). In B, C, W-135, and Y account for nearly all invasive disease. one series of patients presenting with a first episode of Worldwide, type A is responsible for most large epidemics, meningococcemia, 30% had either inherited or acquired but in the United States, serotypes B and C account for deficiencies of complement (4). In addition to comple- approximately 90% of invasive infections. Most people ment deficiencies, deficiencies of immunoglobulin IgG, exposed to an infected individual will become colonized IgG subclass 2, and IgA have been described in patients in the upper respiratory tract. There is an approximately with meningococcal infections (9,10). 5% chance of invasive infection developing in household The clinical manifestations of meningococcal infection contacts in the first 60 days after exposure. Most of these are varied. Tracheobronchitis, conjunctivitis, genital tract occur in the first week (2). Thus, treatment of close con- infection, pneumonia, and meningitis may all occur, with tacts of those with invasive infection is warranted. or without septicemia. Bacteremia may be occult. Acute The carrier state for Neisseria meningitidis is common, meningococcemia usually begins with upper respiratory but invasive infection occurs in few individuals. The tract symptoms, progressing to fever, chills, myalgias, organism is able to survive in a carrier state by a number arthralgias, headache, and nausea and vomiting. Menin- of different mechanisms. It may adhere to epithelial cells gococcal meningitis usually presents without distinctive by pili and may produce IgA proteases—factors that clinical features. It may closely resemble viral meningitis. inhibit ciliary activity. The bacterial polysaccharide Bacteremia is not necessarily present. capsule assists in adherence and inhibits phagocytosis (3). Cutaneous fi ndings in meningococcemia are not con- Invasive disease may be precipitated by antecedent viral sistently present. In one series of adult patients, 50% had infections, inhalation of dry, dusty air, or passive smoke no cutaneous fi ndings or clinical evidence of meningitis inhalation, all factors that may disrupt the integrity of (1). When present, skin fi ndings are not specific. They mucosal epithelium (3). Immunologic response to menin- may include a morbilliform eruption, urticarial papules gococcal disease utilizes all three components of the com- and plaques, petechiae, or purpuric patches (Figure 29.1). plement pathway, the classical pathway, the alternative Morbilliform eruptions, papules and urticarial plaques pathway, and the mannose-binding lectin pathway. may occur early in the disease, and then purpura subse- Patients with inherited defects of the terminal compo- quently develops. Small purpuric necrotic papules and nents of complement C6-C8 (4,5), properdin (6), and vesicles may occur in any anatomic site. These usually genetic variants of mannose-binding lectin (7) are suscep- represent septic or immune complex vasculitis. Broad tible to Neisserial infections, including fulminant or areas of purpura and necrosis are more likely to be mani- chronic meningococcemia. Acquired deficiencies of festations of purpura fulminans, an ominous presentation FIGURE 29.1. Meningococcemia: purpuric papules of the leg extremities. 29. Meningococcemia and Purpura Fulminans 139 FIGURE 29.2. Purpura fulminans: extensive purpuric necrotic patches. of sepsis-associated disseminated intravascular coagula- with HIV infection or deficiencies of complement or tion (Figure 29.2). Such cases may be rapidly fatal, and immunoglobulin (11,12). in the setting of adrenal hemorrhage are referred to as The diagnosis of meningococcal infection is made from Waterhouse-Friderichsen syndrome. Early literature mis- isolation of the organism from usually sterile sites such as took manifestations of sepsis for adrenal insufficiency due blood or cerebrospinal fluid. Surface cultures, especially to adrenal hemorrhage. Most patients with this syndrome those from oropharynx, are not useful because of high have elevations in cortisol (2). rates of carriage in the general population. Blood drawn In the child presenting with fever and a purpuric erup- from puncture wounds of purpuric lesions is reported to tion, one must be vigilant for the possibility of meningo- have a high yield for organisms by Gram’s stain (13). The coccemia. However, in a series of such patients, bacterial organism may be found in Gram’s stains of biopsy speci- sepsis comprises about 12% of the total, and of those, mens of skin lesions or even on the peripheral blood smear meningococcemia accounts for approximately two- (14). Rapid serologic tests are available to detect Neisseria thirds (2). Most children with fever and purpura have meningitidis capsular polysaccharide antigen. These may viral infections, particularly enterovirus. Enterovirus may be particularly useful for CSF or if treatment has been cause aseptic meningitis, resulting in a clinical presenta- instituted. tion similar to that of meningococcemia. The differential Fulminant sepsis may develop rapidly in meningococ- diagnosis also includes infection with parvovirus B19, cemia. Endotoxin is a critical component of host immune Epstein-Barr virus, cytomegalovirus, as well as endocar- activation, and its levels correlate with the severity of ditis, gonococcemia, typhus, drug eruption, and other disease. Serotype C frequently has fulminant manifesta- forms of systemic vasculitis such as Henoch-Schönlein tions, probably because it has the highest production of purpura. endotoxin of any of the serotypes. In the circulation, CD14 A chronic form of meningococcemia also occurs, on the surface of monocytes and endothelial cells is the and generally presents with a less fulminant course and principal receptor for endotoxin. The interaction causes variable skin fi ndings. These include macules, papules, production of pro-inflammatory cytokines such as TNF- erythema-nodosum-like lesions, or palpable purpura due α and IL-1β, which are important inflammatory media- to small vessel neutrophilic vasculitis. However, cutane- tors in sepsis (3). Neutrophils are activated via endotoxin ous involvement is not a constant feature of the disease, and complement to produce proteases that result in tissue particularly in adults. Other manifestations include fever, damage. malaise, myalgias, and arthralgias. Symptoms may persist Complications of meningococcal sepsis may include for weeks prior to diagnosis. Chronic meningococcemia septic arthritis, pericarditis, and endocarditis. One par- may occur in immunocompetent individuals or those ticularly deadly complication of meningococcemia is 140 Deadly Dermatologic Diseases purpura fulminans, which occurs in 15%–25% of patients C

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