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 60-1) and to increased survival after diagnosis. This chapter focuses on infectious complications in immunocompromised children. See also Section 20 for hematologic and oncologic emergencies.
TABLE 60-1The 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) | 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 60-4 | 15–19-year-olds are one of highest risk groups |
| Chemotherapy | 15/100,000 | B cells, T cells | 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 60-2 | Autologous versus allogeneic transplants need to be differentiated |
| Solid organ transplantation | Variable | B cells, T cells | See Table 60-2 | Varying levels of immunosuppression are used for different solid organs and at different times after transplantation |
Certain infections are more common in varying time periods after solid organ transplant (SOT) (Table 60-2).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 60-3).
TABLE 60-2Most 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 | |
| Postoperative 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 |
TABLE 60-3The Most Common Pathogens seen in Immunocompromised Children, with Emphasis on Differences in Clinical Manifestations, Diagnosis, and Treatmenta
| 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 |
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