February 1997
NEWARK, N.J. — For children with immune deficiencies resulting from HIV, transplants or abnormalities of B- or T-lymphocyte function, the incidence of pneumonia puts them at high risk for developing respiratory failure. The challenge for pediatricians is to expedite the initiation of an evaluation and subsequent therapy, which can often be crucial to the survival of these patients, said George McSherry, MD, section chief of pediatric infectious diseases in the division of allergy, immunology and infectious disease at the Children's Hospital of New Jersey in Newark.
McSherry summarized considerations for the diagnosis and treatment of pneumonia pathogens such as Pneumocystis carinii, cytomegalovirus (CMV) and general bacterial infections in the immunocompromised child, at a meeting sponsored by the American Academy of Pediatrics.
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It is important to recognize that the immunocompromised child with pneumonia may have an unusual clinical presentation, McSherry said. For these patients, fever may be absent. While a productive cough and hypoxemia are likely, there may not be any auscultatory findings upon a physical exam, he warned. In general, a chest x-ray will show an interstitial or alveolar pattern.
The fact that certain immunodeficiencies are associated with a known group of pneumonias is also notable at initial presentation, McSherry said. For example, severe combined immune deficiency (SCID) is associated with P. carinii pneumonitis [PCP], cytomegalo virus [CMV] pneumonia and measles. "It's not unusual because of the B-cell abnormalities associated with SCID for a SCID patient to develop severe, recurrent bacterial pneumonias and sepsis," he added.
Patients with DiGeorge's syndrome, an abnormality of T-lymphocyte function, are more susceptible to viral pneumonias and PCP. Among the viruses, adenovirus, herpes simplex and CMV are major problems. With Wiskott-Aldrich syndrome, an X-linked disease, viral pneumonias and PCP are most frequently encountered, McSherry said.
In the other arm of the immune system, patients with Bruton's agammaglobulinemia and common variable immune deficiency — two of the B-cell immune deficiencies — tend to have problems with encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae.
For children with HIV — the most frequent cause of immune deficiency that pediatricians face — PCP is the most common opportunistic infection. Bacterial infections, by the organisms seen commonly in normal children, and viruses, particularly measles and CMV, are also problematic, said McSherry.
"Another consideration when looking at lung disease and children with HIV infection is the fact that approximately 80% will have some problem with lung disease some time during their disease course," McSherry said. Chronic infections such as pulmonary lymphoid hyperplasia-lymphoid interstitial pneumonia (LIP) are the most common.
McSherry also described infections common to transplant patients. "What we find in transplant patients is the type of infections they get vary depending on when after transplantation they become infected, which basically mirrors the ability of various parts of the immune system to heal itself after a transplant. For example, mucosal immunities heal early, followed by neutrophil numbers and function, followed finally by B- and T-lymphocyte immunity," he said.
As a result, for the first 30 days after transplant, herpes simplex virus, fungi, gram-positive and gram-negative bacteria can pose problems, McSherry said. Between 30 and 100 days post-transplant, viruses such as adenovirus and CMV are threatening, as are Aspergillus and P. carinii. More than 100 days after a transplant, varicella virus, encapsulated bacteria and Staphylococcus aureus are potential problems.
For immunocompromised children with pneumonia, McSherry emphasized the importance of immediate evaluation and empiric therapy because of the risk for respiratory failure. There should be a similar urgency, he said, in the early diagnosis of patients with congenital immune deficiency.
"Oftentimes, we lose precious time while we're working out the differential diagnosis of the constellation of signs and symptoms [of an immune deficiency]. We sort of put the immune system on the back burner for a while, and children or infants with immune deficiency will end up with a much more complicated course. They really don't have that much time or the luxury to wait," McSherry warned.
For a patient with a known immune deficiency and respiratory signs and symptoms, McSherry advised consideration of the patient's immune deficiency course, history of infections and exposures to diseases such as measles and varicella. In addition, he recommended confirmation of current medications, the use of intravenous immunoglobulin and adherence to medications and PCP prophylaxis.
"Finally, it's very important to emphasize that sometimes what we can see on the outside can help us on the inside. So, careful physical exam is always indicated," he said.
Typical laboratory tests include complete blood count, electrolyte chemistry, blood culture and chest radiograph. According to McSherry, for children old enough to cooperate, a sputum exam assessed by a Gram's stain and a culture can be extremely helpful. In addition, GMS silver stain, Giemsa's stain and toluidine blue stain are very effective for pneumocystis. Immunofluorescent antibodies and polymerase chain reaction (PCR) are also very reliable, require less time than staining and provide similar sensitivity, although neither is widely available, he said.
McSherry identified three invasive procedures used for the immunocompromised patient: bronchoscopy with bronchoalveolar lavage (BAL), bronchoscopy with BAL and transbronchial biopsy, and open lung biopsy.
BAL, which can be performed quickly and is generally well-tolerated, can be extremely sensitive for organisms such as P. carinii, Legionella, CMV and Mycobacterium tuberculosis. "A key point here is the fact that its negative predictive value really has not been established such that if you get a negative BAL, there are no organisms identified," McSherry said.
When other attempts at diagnosis and therapy have failed, open lung biopsy is a last resort. Though the procedure has a sensitivity range of 60% to 80%, it can be risky. "Depending on how sick the patient is, the mortality can be as high as 23%, although in the hands of a good, skilled pediatric surgeon, earlier on in an infectious process or a disease process, it tends to be very effective with a low morbidity and low mortality," he said.
Considerations for empiric therapy must be made on a case-by-case basis, with pediatricians evaluating the individual patient, where they are in the country and what pathogens they see most frequently, McSherry advised. "Generally, it includes some broad-spectral coverage, an extended-spectrum cephalosporin, perhaps vancomycin, or, depending on the presentation, trimethoprim-sulfamethoxazole."
When Pneumocystis carinii pneumonia is a consideration, IV trimethoprim-sulfamethoxazole (TMP-SMX) and a broad spectrum antibiotic are the first options for any immunodeficient patient. In cases where TMP-SMX doesn't work or there's an allergic response, McSherry recommended IV pentamidine as the best option. In addition, methylprednisolone has been used successfully for HIV patients in increasing survival and decreasing morbidity, he said.
For CMV, diagnosis is by viral isolation, PCR or by finding histopathologic evidence of infection. "Depending on which type of immunodeficient patient you're dealing with, where you find it and how you find it has different meanings," McSherry said. For HIV patients, a positive CMV culture and histopathologic evidence of infection in the absence of another pathogen is recommended before initiating treatment with either ganciclovir or foscarnet; for febrile transplant patients, when CMV is grown, immediate therapy is the rule.
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