Boy With Cough, Dyspnea, and Fever

For the past week, a 16-year-old boy has had a progressivelyworsening dry, irritating cough; dyspnea on exertion;and intermittent fever (temperature up to 38.3^oC[101^oF]) and chills. During the past 24 hours, he hashad no appetite and has vomited greenish material 3 or4 times.Six years previously, a renal biopsy confirmed adiagnosis of systemic lupus erythematosus. This conditionwas complicated by hypertension and chronic renalfailure, for which hemodialysis was recently started.The boy's medications for the last 4 years have includedprednisone, 25 mg/d; nifedipine, 60 mg bid; andchloroquine, 200 mg qd. He also takes aspirin, 80 mgqd; citrate/citric acid solution, 30 mg tid; Nephro-viteB vitamins with vitamin C qd; fluconazole, 200 mg qd;erythropoietin, 10,000 units subcutaneously 3 times/wk.The patient denies chest pain,hemoptysis, palpitations, ankleswelling, hematemesis, melena, andabdominal pain. He has no headaches,visual problems, weakness,paresthesias, seizures, or syncope.There is no history of rashes, adenopathy,weight change, urinarysymptoms, or contact with sickpersons.History. The patient adheresto his medical regimen. He is allergicto penicillin. He does not smoke,drink alcohol, or use recreationaldrugs; he is sexually inactive. Thereis no history of blood transfusion orforeign travel.Examination. This obese, paleyoung man is in moderate respiratorydistress. His temperature is38.3^oC (101^oF); heart rate, 112beats per minute and regular; respirationrate, 28 breaths per minute;blood pressure, 160/90 mm Hg. Hydrationstatus is good. There aresigns of corticosteroid toxicity, includingfacial puffiness, buffalohump, easy skin bruisability, andstriae. There is no palpable lymphadenopathyor thyroidomegaly andno icterus or thrush. Mild pittingedema of the legs is noted. Chesthas normal contours; both sidesmove equally well. Trachea is centrallylocated. Chest is resonant to percussion except at the right base. Harsh bronchovesicularbreath sounds are audible bilaterally with coarserales at the right mid-zone and base. Jugular vein pulseis normal; peripheral pulses are easily felt. Apex beatis within normal limits. Heart sounds are normal withno gallop. A grade 2 musical systolic murmur is heardthroughout the precardium. Abdomen is soft and benign,with no organomegaly, fluid, or tenderness. Resultsof the neurologic examination are normal.Laboratory studies. White blood cell count is18,400/μL, with 82% polymorphonuclear leukocytes,12% lymphocytes, 4% eosinophils, and 2% monocytes.Hemoglobin level, 9.2 g/dL; platelet count, 502,000/μL;erythrocyte sedimentation rate, 110 mm/h. Serum sodiumlevel, 133 mEq/L; potassium, 3.4 mEq/L; chloride,96 mEq/L. Blood urea nitrogen level, 42 mg/dL; serumcreatinine level, 2.9 mg/dL. Results of 2 blood culturesare negative.An ECG shows sinus tachycardia with left ventricularhypertrophy. Sputum examination: Gram stainingshows multiple polymorphonuclear neutrophils. Arterialblood gases: pH, 7.4; PaCO₂, 32 mm Hg; PaO₂, 65 mmHg; oxygen saturation, 90% on room air. An echocardiogramshows evidence of mild aortic regurgitation but novegetation.A bronchoscopy with bronchoalveolar lavage (BAL)is performed. A gram-stained specimen and the chestradiograph are shown.In view of the clinical picture and the abnormalitiesevident in these images, what is the likely cause ofthe patient's disorder?A.Pneumocystis pneumonia
B. Pulmonary tuberculosis
C. Nocardiosis
D. Candidal pneumonia
E. Staphylococcal pneumonia
NOCARDIOSIS: AN OVERVIEW
Nocardiosis is an uncommon suppurative bacterialinfection caused by the aerobic bacillus Nocardia asteroides,a non-spore-forming organism that is ubiquitousin soil, organic matter, and water. The infection usuallyarises from direct inoculation of skin or soft tissue or byinhalation. Nocardiosis, which may be acute or chronic,has been increasingly reported in immunocompetentpatients. Two characteristics that distinguish nocardiosisare its ability to disseminate to virtually any system--particularly the CNS--and its tendency to relapseor progress despite appropriate therapy.CLINICAL MANIFESTATIONS
Nocardiosis occurs in all age groups; the incidenceis higher among older adults and men.Predisposing factors include lymphoreticular malignancy;organ transplantation; prolonged high-dose corticosteroidor other immunosuppressive therapy; underlyingpulmonary disease (such as pulmonary proteinosis);disorders of cell-mediated immunity, including HIV infection;injection drug use; uncontrolled diabetes; and alcoholabuse.The hallmark of nocardiosis is the diversity of itsclinical manifestations, which include pulmonary, extrapulmonary,CNS, and cutaneous involvement.Pulmonary nocardiosis is an invasive disease thatoccurs in more than 40% of patients; onset may be acute,subacute, or chronic. It can manifest as pneumonia, lungabscesses, cavitary disease (such as tuberculosis or fungalinfection), endotracheal inflammatory masses, pleural effusion,or empyema. Common presenting symptoms mayinclude fever, night sweats, fatigue, anorexia, weight loss,dyspnea, cough with purulent expectoration, hemoptysis,and pleuritic chest pain. Radiographic findings includesingle or multiple nodules, lung masses with or withoutcavitation, reticulonodular or intestinal infiltrates, lobarconsolidation, subpleural plaques, and pleural effusion.CNS nocardiosis occurs as a metastatic lesion in33% to 44% of cases. The hallmark manifestation is formationof single or multiple parenchymal abscesses.Patients may present with severe headache, focal neurologicdeficits, seizures, or meningismus with fever.Cutaneous nocardiosis occurs in 4 differentpatterns:

• Primary cutaneous nocardiosis, which may follow aminor trauma or insect bite. It manifests as ulcers, pyoderma,cellulitis, or subcutaneous abscess.
  
• Lymphocutaneous disease. The clinical picture is similarto that of sporothrix infection.
  
• Cutaneous manifestation of disseminated nocardiosis.Skin lesions occur in 2% of cases of generalizeddissemination.
  
• Mycetoma manifests as chronic cutaneous infection.It usually begins as a painless nodule that enlarges andundergoes chronic inflammatory changes and sinustract formation.

Nocardiosis can disseminate from a pulmonary orcutaneous focus to virtually any organ. The most commonlyinvolved extrapulmonary sites are bone, retina,heart, joints, and kidneys.

DIAGNOSIS

Delay in diagnosis is common. A high index of suspicionis essential for prompt diagnosis and treatment.A definitive diagnosis of nocardiosis requires isolationand identification of the organism from a clinical specimen,whether from sputum, BAL fluid, tissue, or culturedmaterial.

TREATMENT

Without specific therapy, invasive nocardiosis canbe fatal. Successful treatment includes administrationof antibiotics in conjunction with surgical drainage anddebridement.Sulfonamides have been the mainstay antibiotics;

TMP-SMX

is considered the drug of choice. The recommendedinitial dose is 5 to 10 mg/kg/d of

TMP

and25 to 50 mg/kg/d of SMX in 2 to 4 divided doses. Higherdoses (

TMP,

15 mg/kg/d;

SMX,

75 mg/kg/d) aregiven to patients with cerebral abscess, disseminatedinfection, or

HIV

infection. Alternatives include sulfadiazineor sulfisoxazole, 6 to 12 g/d in 4 to 6 divideddoses.Patients who cannot tolerate sulfonamides or whohave refractory infection may be given amikacin, imipenem-cilastatin, tetracycline, ceftriaxone, cefotaxime,or cyclosporine.Clinical improvement is seen in about 3 to 10days. Parenteral therapy may be changed to an oralformulation after 1 to 6 weeks, depending on the clinicalresponse.Patients with cutaneous nocardiosis are treated for1 to 3 months; those with pulmonary or disseminatedinfection are treated for 6 to 12 months.Low-dose prophylaxis may have to be maintainedindefinitely after the initial course of therapy in patientswho are immunosuppressed or who are receiving corticosteroidsor other immunosuppressive agents orchemotherapy.

References:

FOR MORE INFORMATION:

• Baracco GJ, Dickinson GM. Pulmonary nocardiosis. Curr Infect Dis Rep. 2001;3:286-292.
  
• Lerner PI. Nocardiosis. Clin Infect Dis. 1996;22:891-905.
• McNeil MM, Brown JM, Hutwagner LE, Schiff TA. Evaluation of therapy forNocardia asteroides complex infections. Infect Dis Clin Pract. 1995;4:287-295.
• Menendez R, Cordero PJ, Santos M, et al. Pulmonary infection with Nocardiaspecies: a report of 10 cases and review. Eur Respir J. 1997;10:1542-1546.
• Mok CC, Yuen KY, Lau CS. Nocardiosis in systemic lupus erythematosus.Semin Arthritis Rheum. 1997;26:675-683.
• Threlkeld SC, Hooper DC. Update on management of patients with Nocardiainfection. Curr Clin Top Infect Dis. 1997;17:1-23.