Chapter 59: Evaluation and Management of the Immunocompromised Patient

Andrea T. Cruz

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AMA Citation
Cruz AT. Cruz A.T. Cruz, Andrea T.Evaluation and Management of the Immunocompromised Patient. In: Schafermeyer R, Tenenbein M, Macias CG, Sharieff GQ, Yamamoto LG. Schafermeyer R, Tenenbein M, Macias C.G., Sharieff G.Q., Yamamoto L.G. Eds. Robert Schafermeyer, et al.eds. Strange and Schafermeyer's Pediatric Emergency Medicine, 4e New York, NY: McGraw-Hill; 2014. http://accessemergencymedicine.mhmedical.com/content.aspx?bookid=1345&sectionid=72124330. Accessed April 26, 2018.

MLA Citation
Cruz AT. Cruz A.T. Cruz, Andrea T.. "Evaluation and Management of the Immunocompromised Patient." Strange and Schafermeyer's Pediatric Emergency Medicine, 4e Schafermeyer R, Tenenbein M, Macias CG, Sharieff GQ, Yamamoto LG. Schafermeyer R, Tenenbein M, Macias C.G., Sharieff G.Q., Yamamoto L.G. Eds. Robert Schafermeyer, et al. New York, NY: McGraw-Hill, 2014, http://accessemergencymedicine.mhmedical.com/content.aspx?bookid=1345&sectionid=72124330.

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High-Yield Facts

Fever in the immunocompromised child is a medical emergency. Prompt evaluation and administration of antibiotics can decrease morbidity and mortality.
Patients on chronic corticosteroids may also require stress dose steroids when febrile.
Children with B cell immunodeficiencies are at risk for encapsulated pathogens. Children with T cell defects may present with chronic or severe viral infections, Pneumocystis jirovecii pneumonia, and recurrent bacterial infections. Children with phagocyte defects present with recurrent infections caused by pyogenic bacteria. Children with complement deficiencies present with encapsulated and pyogenic pathogens.
Acute HIV infection should be suspected in the adolescent with fever, malaise, diffuse lymphadenopathy, pharyngitis, oral ulcers, and a maculopapular rash

The number of immunocompromised children seen in the emergency department (ED) is increasing due to improved detection of some primary immunodeficiencies (PIs) (Table 59-1) and to increased survival after diagnosis. This chapter will focus on infectious complications in immunocompromised children. See also Section 20 for hematologic and oncologic emergencies.

TABLE 59-1The Most Common Immunodeficiencies and Immunocompromising Conditions in the United States

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TABLE 59-1 The Most Common Immunodeficiencies and Immunocompromising Conditions in the United States

Disease	Frequency	Defect(s)	Most Common Opportunistic Infections	Comments
Primary Immunodeficiencies
Severe combined immunodeficiency (SCID)	1/50,000–1/500,000	B cells, T cells	Adenovirus, CMV, EBV, HSV, influenza, measles, norovirus, PCP, rotavirus, RSV, VZV	Lymphatic tissue absent
Ataxia-telangiectasia	1/40,000–1/100,000	B cells, T cells	Recurrent sinopulmonary infections (various organisms described), bronchiectasis	High rate of malignancies
Wiskott–Aldrich	1/100,000	B cells, T cells	Encapsulated organisms (e.g., pneumococcus, meningococcus, H. influenzae), CMV, molluscum, VZV	Associated with lymphoma and autoimmune disease; eczema, thrombocytopenia
Common variable immunodeficiency	1/25,000	B cells	Sinopulmonary infections, chronic gastroenteritis including giardiasis	Poor response to immunizations; lymphatic tissue present and often hypertrophied
Agammaglobulinemia	1/340,000	B cells	Encapsulated bacteria (pneumococcus, Group B streptococci, H. influenza, Pseudomonas, Klebsiella, meningococcus), S. pyogenes. Recurrent otitis media, sinusitis, pneumonia are the most common infections; sepsis, osteomyelitis, and septic joints are also seen	Scant tonsils and adenoids in patient with appreciable peripheral lymph nodes
IgA deficiency	1/333	B cells	Recurrent sinopulmonary infections, often with encapsulated bacteria (pneumococcus, meningococcus, Klebsiella, Pseudomonas, H. influenzae); Giardia and other gastrointestinal infections	Anaphylaxis to blood or IVIG
DiGeorge	1/5,000	T cells	Sinopulmonary infections. Less than 1% have profound immunosuppression (SCID-like)	Hypocalcemic; thymic hypoplasia
Hyper-IgE (Job's)	Unknown	Phagocytes	Staphylococcal and candidal infections of skin, lungs. Invasive pulmonary infection with PCP, Aspergillus, and Nocardia reported	Coarse facies, eczema, failure to shed primary teeth. Serum IgE often >2000 IU/mL
Lymphocyte adhesion deficiency (LAD)	1/100,000	Phagocytes	Recurrent infections of skin, mucosal surfaces; periodontitis	Delayed separation of umbilical cord seen; leukocytosis seen, despite lack of pus formation
Chronic granulomatous disease (CGD)	1/220,000–1/500,000	Phagocytes	Catalase-positive organisms: diphtheria, Listeria, Nocardia, staphylococci, TB, multiple gram-negative bacilli; Aspergillus, Cryptococcus	Perirectal abscesses and invasive Serratia should prompt evaluation for CGD
Chédiak–Higashi	Unknown	Phagocytes	Staphylococci and other catalase-positive organisms (see above)	Congenital neutropenia; oculocutaneous albinism, progressive neurological deterioration (Parkinsonian)
Asplenia (functional, anatomical)	1/30–1/5000	Phagocytes	Encapsulated organisms (pneumococcus, meningococcus, Group B streptococci, Salmonella, Pseudomonas, Klebsiella, H. influenzae)	Please see Section 20 on hematologic emergencies
Shwachman-Diamond	1/75,000	Phagocytes	Lower respiratory tract infections, dental abscesses, recurrent otitis media	Congenital neutropenia, pancreatic insufficiency, skeletal anomalies, increased risk of malignancy
Acquired Immunodeficiencies
Human immunodeficiency virus (HIV)	4/100,000	T cells	See Table 4	15–19-year-olds are one of highest risk groups
Chemotherapy	15/100,000	B cells, T cells	Please see Chapter 108 on oncologic emergencies	The degree and duration of immunosuppression varies by malignancy
Bone marrow transplantation	Variable	B cells, T cells	See Table 2	Autologous versus allogeneic transplants need to be differentiated
Solid organ transplantation	Variable	B cells, T cells	See Table 2	Varying levels of immunosuppression are used for different solid organs and at different times after transplantation

CMV, cytomegalovirus; EBV, Epstein–Barr virus; HSV, herpes simplex virus; PCP, Pneumocystis jirovecii pneumonia; RSV, respiratory syncytial virus; VZV, varicella zoster virus; IVIG, intravenous immunoglobulin; TB, M. tuberculosis.

Solid Organ Transplant Recipients

Certain infections are more common in varying time periods after solid organ transplant (SOT) (Table 59-2).¹ Pathogens can be conceptualized as acquired from the donor, native flora that can reactivate or worsen after immunosuppression, postoperative infections, and newly acquired opportunistic infections (OIs) due to immunosuppression (Table 59-3).

TABLE 59-2Most Common Infections in Transplant Recipients as a Function of Time Since Transplant

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TABLE 59-2 Most Common Infections in Transplant Recipients as a Function of Time Since Transplant

Transplant	0–1 month	1–6 months	>6 months
Solid Organ	Donor-derived infection: Viral: CMV, EBV, HHV-6, HIV, HSV, lymphocytic choriomeningitis virus, rabies, VZV, West Nile virus Fungal: Aspergillus, Candida, Coccidioidomycosis, Cryptococcus, Histoplasmosis Bacterial: bacteremia (Salmonella and multiple other pathogens identified), meningococcus, NTM, syphilis, TB Parasitic/Protozoal: Babesiosis, malaria, Strongyloides, Toxoplasma	Viral: adenovirus, CMV, EBV, HSV, influenza, Varicella zoster virus, hepatitis viruses, BK virus (the latter primarily in renal transplant recipients)	Viral: CMV (CNS, retinitis, colitis), EBV (causing post-transplant lymphoproliferative disorder, PTLD), HSV (CNS), polyoma viruses (causing progressive multifocal leukoencephalopathy)
	Recurrent infection present prior to transplantation in donor or recipient: hepatitis B, C, pulmonary aspergillosis	Fungal: Cryptococcus, PCP	Fungal: Aspergillus, Mucor species
	Post-operative infectious complications:^a wound infections, VAP, UTI, CVC infections, superinfection of grafted tissue, C. difficile	Bacterial: C. difficile, Nocardia, TB	Bacterial: pathogens causing community-acquired pneumonia; Nocardia
		Parasitic/Protozoal: Strongyloides, Toxoplasma, Chagas disease
	0–3 weeks	3 weeks–3 months	>3 months
Bone marrow/stem cell	Recurrent infection present prior to transplantation in recipient: S. aureus, pneumococcus, gram-negative enterics, Aspergillus, Candida, adenovirus, influenza, RSV	Viral: adenovirus, CMV, HHV-6, influenza, RSV	Viral: adenovirus, CMV, EBV, HHV-6, influenza, RSV, varicella zoster virus
		Fungal: Aspergillus, PCP	Fungal: Aspergillus, PCP
		Bacterial: S. aureus, pneumococcus, gram-negative enterics	Bacterial: encapsulated pathogens (pneumococcus, meningococcus, Pseudomonas, H. influenzae, S. aureus)
		Parasitic/Protozoal: Cryptosporidium, Giardia	Parasitic/Protozoal: Cryptosporidium, Giardia

CMV, cytomegalovirus; HHV, human herpesvirus type 6; HIV, human immunodeficiency virus; HSV, herpes simplex virus; NTM, non-tuberculous mycobacteria; TB, Mycobacterium tuberculosis; CNS, central nervous system; PCP, Pneumocystis jirovecii pneumonia; VAP, ventilator-associated pneumonia; UTI, urinary tract infection; CVC, central venous catheter; RSV, respiratory syncytial virus.

^aMany may be due to antibiotic-resistant pathogens given the recipient's antibiotic exposure history.

TABLE 59-3The Most Common Pathogens seen in Immunocompromised Children, with Emphasis on Differences in Clinical Manifestations, Diagnosis, and Treatment^a

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TABLE 59-3 The Most Common Pathogens seen in Immunocompromised Children, with Emphasis on Differences in Clinical Manifestations, Diagnosis, and Treatment^a

Pathogen	Symptoms/Site	Diagnosis	Treatment	Notes
Bacteremia (multiple pathogens)	Fever, chills, shock	Blood culture	Broad-spectrum antibiotics	Use prior culture results to guide empiric therapy
Pneumonia (multiple pathogens)	Fever, cough, dyspnea	Radiograph, blood culture, viral studies	Broad-spectrum antibiotics	Evaluation for both bacterial and viral pathogens is important
C. difficile	Fever, painful diarrhea with blood and mucus	Stool toxin assay	Metronidazole; oral vancomycin as 2nd line	Up to one-third of infants are asymptomatically colonized
M. tuberculosis (TB)	Fever, chills, cough, weight loss; night sweats and hemoptysis are uncommon in children	Culture, PCR, tuberculin skin test, IGRA	Isoniazid, rifampin, pyrazinamide, ethambutol	Children infrequently are culture positive; index of suspicion must be high to make the diagnosis
Nontuberculous mycobacteria (NTM)	Can cause pulmonary, skin/soft tissue, lymphadenopathy, and disseminated disease	Culture	Varies by species	Differentiating colonization from disease can be challenging
Nocardia	Lymphocutaneous disease in normal hosts; pulmonary, CNS, and skin disease seen in immunocompromised children	Culture; bacteria are variably acid-fast	Trimethoprim-sulfamethoxazole; add amikacin for CNS or other life-threatening disease	Need to ask lab to hold cultures for several weeks to allow this indolent pathogen to be isolated
Aspergillus	Pulmonary, sinus, CNS, or skin involvement with associated thromboses	Culture, silver stain of biopsy specimen	Amphotericin	Can see halo sign on chest CT
Coccidioidomycosis	Fever, chest pain, dyspnea, weight loss; skin findings and arthralgia may be only signs in children	Serology, culture	Amphotericin	Travel history is important: in the United States, endemic in the Southwest
Cryptococcus	Indolent meningitic symptoms; skeletal and skin nodules can be seen	Serum and CSF antigen; culture	Amphotericin + flucytosine	Can have minimal CSF pleocytosis
Histoplasmosis	Fever, chest pain, dyspnea, weight loss, erythema nodosum	Serology, culture, urinary antigen	Amphotericin	Antigen testing insensitive for pulmonary histoplasmosis in immunocompromised persons
Pneumocystis jirovecii	Subacute presentation with fever, nonproductive cough, dyspnea; hypoxemia often noted	Silver stain; CXR	Trimethoprim-sulfamethoxazole	LDH often very elevated; CXR shows diffuse reticulonodular pattern
Adenovirus	Hemorrhagic cystitis, pneumonia, hepatitis, conjunctivitis, colitis	Viral culture; rapid assays have poor sensitivity	Cidofovir for disseminated disease	Virus can be shed for months after initial infection
BK virus	UTI symptoms, hemorrhagic cystitis	PCR	Supportive	Can be associated with chronic renal failure
Cytomegalovirus (CMV)	Pneumonia, colitis, retinitis, hepatitis	PCR, antigenemia, serology	Ganciclovir	Like all herpes viruses, CMV can reactivate after periods of latency
Epstein–Barr virus (EBV)	Fever, influenza-like illness, Guillian–Barré, meningoencephalitis, PTLD, hemophagocytic syndrome	PCR, serology	Supportive	Very elevated ferritin can be seen with PTLD; can see primary or reactivation infection
Herpes simplex virus (HSV)	Severe dermatologic findings, eczema herpeticum; disseminated HSV less common	Culture, PCR	Acyclovir	Varied CNS presentations seen: meningoencephalitis, Bell palsy, ascending myelitis
Influenza	More severe symptoms than influenza in normal hosts	Viral culture, rapid assays, PCR	Oseltamivir	Higher rates of hospitalization seen in children with malignancies and hemoglobinopathies
Parvovirus	Fever, rash; aplastic crisis, occasionally with involvement of other cell lineages	Serology	Supportive	Can cause crisis in children with hemoglobinopathies
Varicella zoster virus (VZV)	Can see hemorrhagic VZV or reactivation as shingles	Direct fluorescent antibody (DFA) testing	Acyclovir (not as effective for VZV as for HSV)	Atypical presentations of chicken pox seen in immunocompromised children
Babesiosis	Fever, chills, headache, malaise, pallor (mimics malaria)	Maltese cross on peripheral smear	Quinine + clindamycin	Overwhelming parasitemia seen in asplenic patients
Cryptosporidium	Nonbloody, watery diarrhea (lasts weeks), abdominal pain, weight loss; pulmonary, biliary tract, and disseminated disease can be seen in the immunocompromised	Stool antigen testing	Nitazoxanide	Shedding can be intermittent, requiring collection of several stool specimens
Giardia	Watery nonbloody diarrhea, abdominal pain and distension, flatulence	Stool antigen testing	Nitazoxanide	More common in persons with humoral immunodeficiencies
Malaria	Fever, chills, headache, malaise, pallor	Thick, thin peripheral smears	Quinine + clindamycin	P. falciparum has higher morbidity/mortality than other plasmodial species.
Strongyloides	Pulmonary infiltrates, sepsis, meningitis (from translocation of Gram-negative enterics across the gut)	Visualization of larvae in the stool; serologies cross-react with filariae	Ivermectin or thiabendazole	Eosinophilia seen during tissue migration phase; auto-inoculation seen in immunocompromised hosts
Toxoplasmosis	Encephalitis, pneumonia, disseminated disease	Serology	Pyrimethamine + sulfadiazine	IgM response poor in immunocompromised patients

PCR, polymerase chain reaction; IGRA, interferon gamma release assay; CT, computed tomography; CSF, cerebrospinal fluid; CXR, chest radiograph; LDH, lactate dehydrogenase; UTI, urinary tract infection; PTLD, post-transplant lymphoproliferative disorder.

^aThe most common opportunistic pathogens in HIV-infected children are described separately (Table 4)

Recurrent pneumonia caused by typical or atypical pathogens (e.g., adenovirus, cytomegalovirus [CMV]) can be seen following lung transplantation. UTIs have been described almost half of children after renal transplantation, commonly with Escherichia coli and Klebsiella. BK virus and other polyoma viruses can cause hematuria or pyuria in renal transplant recipients and can be associated with chronic renal failure and graft loss. Colitis due to viral pathogens (CMV, herpes simplex virus [HSV]) or Clostridium difficile can be seen in small bowel transplant recipients. Bacterial infection of the transplanted organ is less common in heart and liver transplant recipients.

Bloodstream infections (BSI) in the post-transplant period can be secondary to CVC-associated infections, immunosuppression, or from translocation across leaky intestinal walls. In lung transplantation, BSIs are most common in the first month after SOT with the most common organisms being CONS, Pseudomonas, and Candida species.² Although BSIs are also most common early after heart transplantation, gram-negative bacteria predominate over gram-positive organisms; fungal, anaerobic, or cryptococcal BSI account for <10% of cases. Liver transplant recipients are at higher risk of ascending cholangitis and should be covered for gram-positive, gram-negative, and anaerobic pathogens.³

Viral infections contribute to morbidity, mortality, and graft loss in SOT recipients.⁴ The most common virus in the post-transplant period is CMV. Treatment with valganciclovir or ganciclovir in the immediate post-transplant period does not prevent all cases of post-transplant disease or establishment of viral latency. SOT recipients have higher morbidity and mortality with influenza, and graft loss can be seen.⁵ Rapid viral testing has poor sensitivity mandating empiric therapy for SOT recipients with an influenza-like illness during influenza season,⁶ regardless of the rapid test result. Adenovirus can cause hemorrhagic cystitis, pneumonitis, hepatitis, and colitis. The most dreaded post-transplant virus is Epstein–Barr Virus (EBV), which can cause organ-specific pathology (hepatitis, pneumonitis, colitis, marrow dysfunction) or post-transplant lymphoproliferative disease (PTLD). SOT recipients have a risk of malignancy 5 to 10 times higher than the general population, most caused by EBV-associated malignancies, including hemophagocytic syndrome, lymphomas, and leiomyosarcomas.⁴ PTLD symptoms are protean and include constitutional symptoms, isolated or disseminated lymphadenopathy, tonsillar hypertrophy, sore throat, vomiting, diarrhea, GI bleeding, or organ failure. Intussusception in a SOT recipient should trigger an evaluation for PTLD, as the lead point for the intussusception may be GI lymphoid hyperplasia. Cytopenias and elevated ferritin and triglycerides commonly are seen.

OIs seen in SOT recipients include many pathogens seen in other immunocompromised children (Tables 59-2 and 59-3). These may include vaccine-preventable diseases if the child was unable to respond to vaccinations received in the pretransplant period. Although Pneumocystis (PCP) is associated with HIV-infection, transplant recipients accounted for almost 40% of PCP cases in one large series.⁴ Finally, children who have received SOT are at higher risk for autoimmune disease.⁷

The initial ED evaluation of the febrile SOT child should include a CBC, blood cultures (peripheral and from all lumens if child has a central line), rapid viral testing, chest radiograph, and chemistries. Evaluation should be targeted based on the kind of transplant, degree of immunosuppression, time since transplantation (Table 59-2), results of pretransplant serologies, and post-transplant infections. Broad-spectrum antibiotics should be initiated. A third-generation cephalosporin or a semi-synthetic, antipseudomonal penicillin (e.g., piperacillin-tazobactam) would be reasonable. The latter would be of particular use in liver transplant recipients, who are at risk for polymicrobial ascending cholangitis.

Primary Immunodeficiencies

PIs can involve isolated or combined defects in various arms of the immune response. The most common PIs include B cell defects, and the most common organisms seen in these patients are encapsulated bacteria, as seen in asplenic patients. OIs begin as maternal antibodies wane in infants, and can include bacteremia and upper and lower respiratory tract disease. T cell (cellular immune) defects present with prolonged or severe viral illnesses, PCP,⁸ mycobacteria, and fungi. Antibody response can be impaired in patients with T cell defects, making these children at higher risk for some of the same bacterial pathogens seen in children with B cell defects. The complement system targets antigens on the surface of pathogens for destruction by phagocytosis. The best-known complement defect is in the terminal portion of the complement cascade (C5–C9), predisposing to meningococcal disease. Phagocyte defects are associated with invasive disease from an early age with S. aureus, Serratia, Pseudomonas, Aspergillus, and Candida. Phagocyte defects should be suspected in any patient who presents with invasive Serratia, even if this is the first documented infection.⁹

The low prevalence and heterogenous nature of PIs results in few large case series describing infectious etiologies. The most common reasons for hospitalization are gastroenteritis (Giardia, Candida, and Salmonella) and pneumonia.¹⁰

Initial diagnostic evaluation should include a CBC, blood culture, rapid viral studies (or PCR), and chest radiograph. For children with diarrhea, fecal white cells, bacterial and viral stool culture, C. difficile, and Cryptosporidium/Giardia antigen testing should be considered. Cryptosporidium also should be in the differential diagnosis of a PI patient with cholangitis. If PCP is considered, elevated lactate dehydrogenase (LDH) may be the first supportive finding. PCR, when available, has excellent negative predictive value for PCP.¹¹ Broad-spectrum antibiotics targeting the most common bacteria isolated from each class of PI should be promptly begun, tailored to prior culture results. Knowledge of the patient's prophylactic therapy is helpful to potentially narrow the differential diagnosis and to select empiric therapy. For example, if a child is receiving penicillin prophylaxis and presents with pneumonia, ampicillin should not be part of the empiric regimen given the risk of resistance to this class of drugs.

HIV

HIV-infected children may present to the ED with acute HIV infection, OIs (Table 59-4)¹² in undiagnosed HIV, or with established disease. The diagnosis of acute HIV infection should be considered in the adolescent who present to the ED with fever, pharyngitis, oral ulcers, and disseminated lymphadenopathy. The presentation mimics mononucleosis, and often occurs 4 to 8 weeks after the infection, during the “window period” where serologies are negative. Diagnosis is established by polymerase chain reaction (PCR). A CBC may show leukopenia, lymphopenia, and thrombocytopenia. The diagnosis can be made in previously undiagnosed children who have harbored the virus for longer periods of time when they present with failure to thrive, chronic diarrhea, or recurrent upper and lower respiratory tract infections. Examination findings may include nontender parotid enlargement, splenomegaly, disseminated lymphadenopathy, and cachexia. OI types are associated with the CD4 cell count (Table 59-4).

TABLE 59-4The Most Common Opportunistic Infections seen in Children Infected with Human Immunodeficiency Virus (HIV)

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TABLE 59-4 The Most Common Opportunistic Infections seen in Children Infected with Human Immunodeficiency Virus (HIV)

CD4 Cell Count^a			Disease	Symptoms	Diagnosis	Treatment
<12 m	1–5 y	>5 y
≥1500	≥1000	≥500	Recurrent URI, sinusitis, or AOM Lymphadenopathy Parotitis Hepatosplenomegaly	b Nontender, >0.5 cm Nontender, bilateral Nontender	^b N/A N/A N/A	^b N/A (due to viral infiltration) N/A (due to viral infiltration) N/A (due to viral infiltration)
750–1499	500–999	200–499	Same OIs as seen with higher CD4 counts + the following:
			Candidiasis	^b, but more severe and of longer duration; candidiasis involving the lower respiratory tract or esophagus is an AIDS-defining illness (^c)	Culture	Fluconazole
			Kaposi sarcoma^c	Non-tender purplish palpable skin lesions on skin, mouth	Biopsy	Start ARTs
<750	<500	<200	Same OIs as seen with higher CD4 counts + the following:
			Tuberculosis^c	^b, but more often extrapulmonary	Acid-fast culture, tuberculin skin test	Isoniazid, rifabutin, pyrazinamide, ethambutol
			Pneumocystis jirovecii^c	Fever, dyspnea, hypoxemia		Trimethoprim-sulfamethoxazole
			Histoplasma^c, Coccidioidomycosis^c	Fever, dyspnea, chest pain, weight loss	Culture, urine antigen (for Histoplasma), serology	Amphotericin
			Progressive multifocal leukoencephalopathy (PML)^c	Loss of milestones, confusion, seizures, difficulty ambulating	Imaging, history	None
			Toxoplasmosis^c	Fever, seizures, confusion, motor weakness	Serology	Trimethoprim-sulfamethoxazole
			Cryptosporidium, chronic^c	Chronic watery diarrhea, weight loss, vomiting	Stool antigen testing	Nitazoxanide
			Cryptococcal infection	Fever, headache, neck stiffness, memory loss Extrapulmonary cryptococcal infection is an AIDS-defining illness (^c)	Culture, antigen testing	Amphotericin + flucytosine
			CMV (CNS, retinitis)^c	Fever, visual changes, headaches, abdominal pain, diarrhea	Culture, PCR, antigenemia	Ganciclovir
			Mycobacterium avium complex^c	Fever, night sweats, cough, abdominal pain, dyspnea	Culture	Azithromycin, rifampin, ethambutol

URI, upper respiratory tract infection; AOM, acute otitis media; N/A, not applicable; OI, opportunistic infection; AIDS, acquired immunodeficiency syndrome; ART, antiretroviral therapy; CMV, Cytomegalovirus; CNS, central nervous system.

^aYoung infants have higher CD4 counts at baseline than older children. School-aged children have CD4 counts that are in the same range as adults.

^bSame as normal host

In the child already receiving antiretroviral (ART) therapy, knowledge of the most recent CD4 count, adherence with antiretrovirals (ARVs), and receipt of prophylactic medications may help narrow the differential diagnosis. With good adherence, OIs are less common, but these children may present for ART adverse effects. The most common side effects with nucleoside reverse transcriptase inhibitors (NRTIs) are hepatic toxicity, marrow suppression, and hypersensitivity reactions. Non-NRTIs can be associated with hepatotoxicity and rashes. Protease inhibitors are associated with hepatotoxicity, hyperglycemia, rashes, and fat maldistribution.

One opportunistic infection that must be considered in any HIV-infected patient presenting with respiratory symptoms and/or radiographic infiltrates is PCP. PCP can cause subacute pneumonia, quiet tachypnea, and hypoxemia. The classic radiographic finding is a diffuse reticulonodular pattern. Serum LDH is usually very high. Prompt initiation of high-dose trimethoprim sulfamethoxazole can be life-saving. For patients with a Pao2 of <70 mm Hg on room air, adjunctive corticosteroids should be considered.

References

Anaissie D. Overview of infections following hematopoietic cell transplantation. In: Basow DS, ed. UpToDate. Waltham, MA: 2012.

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Mamishi S, Eghbali AN, Rezaei N, Abolhassani H, Parvanech N, Aghamohammadi A. A single center 14 years study of infectious complications leading to hospitalization of patients with primary antibody deficiencies. Braz J Infect Dis. 2010;14:351–355.
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Centers for Disease Control and Prevention. 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Recomm Rep. 1994;43:1–19.

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