Young Man With Fever, Weakness, and Rash

A 24-year-old man who worked ina warehouse is brought tothe emergency department following2 days of high fever with rigors, generalizedweakness, and a purplishrash on both lower legs that had progressedrapidly during the past24 hours. He had become ill about5 days previously, with a worseningsore throat and achiness that did notrespond to over-the-counter lozengesand ibuprofen.He denies contact with ill persons and has no historyof headache, vision problems, photophobia, neck stiffness,seizures, cough, dyspnea, or chest pain. He had vomitedtwice the previous day but has had no hematemesis,melena, or abdominal pain. His appetite has been poor,and he has consumed very little food or drink in the past24 hours. He has no urinary symptoms, but his urinaryoutput is considerably reduced.History. The patient does not use tobacco, alcohol, orillicit drugs and takes no medications. He is not sexuallyactive. He has not had blood transfusions or been tattooed.His mother has diabetes, and his father is hypertensive.Examination. The patient looks very ill. His heartrate is 130 beats per minute and regular; temperature,38.8C (102F); respiration rate, 26 breaths per minute;blood pressure, 100/60 mm Hg. Throat is erythematous;mucous membranes are dry. Purplish ecchymotic lesionsof various sizes are present on the lower legs and buttocks.There is no palpable adenopathy. The feet are puffyand the ankles are swollen. Neurologic examination revealssevere lethargy and slow responses. There is no cranialnerve deficit, and the patient can move all of his extremities.Deep tendon reflexes are sluggish and plantarreflexes are flexor. Neck is supple with no meningealsigns. Jugular venous pulse is normal; apex is well localizedwithin normal limits. Heart sounds are normal.Lungs are clear. Abdomen is soft and nontender with noorganomegaly.Laboratory studies. White blood cell (WBC) count,34,000/L, with 72% polymorphonuclear leukocytes,22% bands, and 6% lymphocytes. Hemoglobin, 12.6 g/dL;platelet count, 92,000/L; erythrocyte sedimentation rate,120 mm/h. Serum sodium, 130 mEq/L; potassium,3.1 mEq/L; chloride, 96 mEq/L; blood glucose, 90 mg/dL.Blood urea nitrogen level, 52 mg/dL; serum creatinine,1.2 mg/dL. Urinalysis reveals trace protein. Chest radiographshows no infiltrates. A lumbar puncture revealscloudy cerebrospinal fluid (CSF); protein level, 148 mg/dL;glucose level, 68 mg/dL; WBC count, 686/L, with 88%polymorphonuclear leukocytes and 12% lymphocytes.Which of the following organisms does the history,physical and laboratory findings, and this Gram-stainedCSF smear implicate as the cause of the patient'sillness?A. Listeria monocytogenesB. Streptococcus pneumoniaeC. Neisseria meningitidisD. Haemophilus influenzaeE. Cryptococcus neoformansWHAT'S WRONG:
The smear shows polymorphonuclear cells withgram-negative diplococci. In a young man with evidenceof sepsis and a purplish, blotchy lower leg rash (Figure),the presence of diplococci, elevated protein levels, andpolymorphonuclear pleocytosis in the CSF strongly suggestsN meningitidis infection, C.Hospital course. The patient is promptly admittedto the ICU and given intravenous fluids, initially at a rateof 250 mL per hour; penicillin G, 4 million units IV every4 hours; rifampin, 600 mg IV every 24 hours; and dexamethasone,10 mg every 8 hours.A blood culture is positive for gram-negative diplococci,which are identified as meningococci. Immunoglobulinand complement levels are normal. HIV test results arenegative.The patient becomes afebrile in the next 72 hours andreceives a 14-day course of intravenous penicillin in thehospital. At discharge, he still has scabbing lesions on hislower legs; however, his other symptoms have resolved.MENINGOCOCCAL MENINGITIS:
AN OVERVIEWMeningococcal meningitis is a major infectious causeof childhood mortality in developed countries; the UScase-fatality rate is 12%. There are approximately 2500 to3000 cases a year in the United States-about 0.9 to 1.5cases per 100,000 population.1 Meningeal disease occursthroughout the year, although more cases are reportedduring the winter and spring months.The rates of disease are highest among infants, butin recent years 23% of cases have occurred in persons betweenthe ages of 12 and 29 years.1 The incidence is higherin African Americans and slightly higher in men than inwomen (1.2:1). The disease can occur sporadically or inepidemic form. Serogroup C is the type predominantlyseen in the United States.PATHOPHYSIOLOGY
Humans are the only natural hosts for meningococci.About 30% of teenagers and 10% of adults carry meningococciin the upper respiratory tract at any given time,although pathogenic strains are found in only 1% of carriers.The organism is transmitted by airborne droplets.Infection is preceded by colonization of the nasopharynx.Meningococci then enter the bloodstream and spread tospecific sites, such as the meninges or joints, or disseminatethroughout the body. Because meningococcal meningitiscan be fatal within hours, accurate diagnosis andrapid treatment are critical.RISK FACTORS
Low socioeconomic status, household crowding,urban residence, and exposure to tobacco smoke arerisk factors for meningococcal infection. In addition,new military recruits who live in barracks and collegefreshmen who reside in dormitories are at heightenedrisk for infection.Underlying immune defects also confer a predispositionto invasive meningococcal disease. These includefunctional or anatomic asplenia, a deficiency of properdinor terminal complement components, and HIV infection.CLINICAL MANIFESTATIONS
Patients with acute meningococcal infection can presentclinically with 1 of 3 syndromes:

• Meningitis (30% to 50% of cases).
• Meningitis with septicemia (40% of cases).
• Meningococcemia without obvious meningitis (7% to 10%of cases).

A nonspecific prodrome of cough, headache, andsore throat often precedes a rapid onset of fever with rigors,arthralgia, and myalgias. Patients with meningococcalmeningitis appear severely ill. They may be tachycardicand hypotensive; temperature may be moderate or veryhigh. In fulminant meningococcemia, the patient becomesvery lethargic, with headache, abdominal pain, and vomiting.Vascular collapse, which may occur within a fewhours, manifests with tachycardia, hypotension, and cool extremities. The triad of headache, confusion, andmeningeal signs suggests meningococcal meningitis.A petechial rash on the axillae, flanks, wrists, and anklesis present in 50% to 80% of patients. Ecchymotic lesionsare seen over the trunk and legs. Rash is generallya sign of septicemia. Rapid enlargement of petechiae andpurpuric lesions may progress to purpura fulminans.In meningitis with septicemia, headache, photophobia,lethargy, neck stiffness, and drowsiness may be present.Seizures may occur in 20% of patients at presentationand in an additional 10% within 72 hours.

¹

Altered mentationand coma may occur in fulminant disease. Meningococcemiais often associated with rapid onset of hypotension,acute adrenal hemorrhage (the Waterhouse-Friderichsensyndrome), and multiorgan failure.Pneumonia develops in 5% to 15% of patients with invasivemeningococcal disease.1 Congestive heart failure,gallop, pulmonary edema, and poor peripheral perfusionmay be present. Disorders associated with meningococcaldisease that are seen much less frequently include conjunctivitis,otitis media, epiglottitis, arthritis, urethritis, andpericarditis.A less common presentation is chronic meningococcemia,a syndrome characterized by episodes of fever,polyarthralgia, tenosynovitis, anorexia, headache, andrash over the course of several months.

DIAGNOSIS

Definitive diagnosis requires culture of meningococcifrom blood, CSF, joint fluid or, occasionally, skin lesions.Blood cultures are positive in 60% to 80% of untreated patients;CSF cultures are positive in 70%.

²

CSF pressures are elevated; elevated protein levels,decreased glucose levels, and predominant polymorphonuclearpleocytosis are characteristic. Gram stain andpolymerase chain reaction testing can identify the gramnegativediplococci. The percentage of polymorphonuclearleukocytes in the blood is usually elevated; thrombocytopeniaoccurs in severe cases. Chest radiography isuseful to evaluate for pneumonia and acute respiratorydistress syndrome. In patients with septicemia, coagulationoften is disturbed, with consumption and loss of clottingfactors.Biochemical disturbances, which are common in fulminantmeningococcemia, include hypokalemia, hypocalcemia,and hypomagnesemia with metabolic and lacticacidosis.

TREATMENT

Effective antibiotics must be administered promptlyin patients with suspected meningococcal disease; fluidand electrolyte balance must also be maintained.The antibiotic of choice in treatment of meningococcalsepticemia or meningitis is penicillin G

(Table).

In patientsallergic to penicillin, alternatives include a third-generationcephalosporin, such as ceftriaxone or cefotaxime.Another option is chloramphenicol. Treatment is given for10 to 14 days. Persons in close contact with patients whohave meningococcal disease are at elevated risk for infection.Agents commonly used for prophylaxis are listed inthe

Table.

References:

REFERENCES:

1.

Rosenstein NE, Perkins BA, Stephens DS, et al. Meningococcal disease.

N Engl J Med.

2001;344:1378-1388.

2.

Salzman MB, Rubin LG. Meningococcemia.

Infect Dis Clin North Am.

1996;10:709-725.

FOR MORE INFORMATION:

Warren HS, Gonzalez RG, Tian D. A 12-year-old girl with fever and coma.

N Engl J Med.

2003;249:2341-2349.