What are the symptoms and treatment options for Pneumocystis jirovecii in immunocompromised children?

Pneumocystis jirovecii Symptoms in Immunocompromised Children

In immunocompromised children, Pneumocystis jirovecii pneumonia (PCP) presents with fever, tachypnea, dyspnea, and cough, with onset that can be either abrupt or insidious, and almost all patients will have tachypnea by the time pneumonitis appears on chest radiograph. 1

Clinical Presentation

Primary Respiratory Symptoms

• Fever, tachypnea, dyspnea, and cough are the cardinal features, with severity varying from child to child 1, 2
• Tachypnea is nearly universal once pneumonitis is visible on imaging, even in patients who are not febrile 1
• Physical examination typically reveals bibasilar rales with evidence of respiratory distress and hypoxia 1

Nonspecific Early Symptoms

• Onset can be insidious with mild cough, dyspnea, poor feeding, and weight loss before progressing to severe disease 1
• These nonspecific symptoms may delay diagnosis, particularly in infants 1

Hypoxemia and Laboratory Findings

• Substantial hypoxia with low arterial oxygen pressure and alveolar-arterial oxygen gradient >30 mm Hg is characteristic 1
• Lactate dehydrogenase (LDH) is often elevated but is not specific for PCP 1, 2
• Serum albumin may be depressed 1

Radiographic Findings

• Bilateral diffuse parenchymal infiltrates with "ground-glass" or reticulogranular appearance are most common on chest radiographs 1, 2
• Earliest infiltrates are perihilar, progressing peripherally before reaching the apical portions of the lung 1
• Chest radiographs may be normal or show only mild parenchymal infiltrates early in disease 1
• High-resolution CT scans demonstrate characteristic ground-glass pattern and are more sensitive than plain radiographs 2
• Rarely, lobar, cavitary, nodular or miliary lesions, pneumothorax, or pneumomediastinum are observed 1

Special Considerations in Pediatric Populations

Age-Specific Risk

• Highest incidence occurs in the first year of life, with cases peaking at age 3-6 months in HIV-infected infants 1, 3
• PCP accounts for 57% of AIDS-defining conditions among infants aged <1 year 1, 3
• **CD4+ cell counts are not a good indicator of risk in infants aged <1 year**; many young infants with PCP have CD4+ counts >1,500/µL 1

Mortality

• Mortality rate is high: 35% of children with PCP died within 2 months of diagnosis in the pre-HAART era 1, 3
• The estimated median survival time was 19 months before availability of HAART therapy 1

Coinfection Complications

• Infants with dual infection with cytomegalovirus (CMV) and P. jirovecii have more severe pneumonic disease and are more likely to require assisted ventilation, receive corticosteroids, or die than those with PCP alone 1

Extrapulmonary Disease

• Extrapulmonary pneumocystosis is uncommon in HIV-infected children (seen in <2.5% of HIV-infected adults) 1
• Can occur without concurrent PCP and at multiple noncontiguous sites including ear, eye, thyroid, spleen, gastrointestinal tract, peritoneum, liver, pancreas, and less frequently adrenal glands, bone marrow, heart, kidney, lymph nodes, meninges, and muscle 1

Diagnosis

• Definitive diagnosis requires demonstration of the organism in pulmonary tissues or fluids 1
• Induced sputum analysis and bronchoalveolar lavage are the diagnostic procedures of choice 2
• Gomori's methenamine-silver stain, Giemsa or Wright's stain, and monoclonal immunofluorescent antibody stains are most commonly used 2, 4
• Polymerase chain reaction (PCR) assays in bronchoalveolar lavage fluid are more sensitive than traditional staining methods 2, 4
• Measurement of (1-3)-β-D-glucan in serum has high negative predictive value in ruling out PJP 4

Treatment Overview

First-Line Treatment

• Trimethoprim-sulfamethoxazole (TMP-SMX) at 15-20 mg/kg/day of the trimethoprim component, divided every 6-8 hours for 14-21 days is the recommended treatment 5, 6, 2, 7, 4

Adjunctive Corticosteroids

• Corticosteroids are recommended for severe PCP with PaO₂ <70 mmHg or alveolar-arterial gradient >35 mmHg 5, 2
• This reduces mortality in HIV-infected patients 5

Alternative Regimens

• Clindamycin (600-900 mg IV every 6-8 hours) plus primaquine (15-30 mg base PO daily) is the preferred alternative when TMP-SMX cannot be used 5
• Pentamidine isethionate 4 mg/kg/day IV over 60-90 minutes is a second-line alternative for patients intolerant of TMP-SMX 5, 8, 2

Critical Pitfalls to Avoid

• Do not delay treatment while awaiting bronchoscopy if PCP is suspected based on clinical presentation and elevated LDH 5
• **Do not rely on CD4+ counts in infants <1 year** as they can be >1,500/µL even with active PCP 1
• Consider CMV coinfection in infants with severe disease, as this worsens prognosis 1
• Check G6PD levels before using primaquine or dapsone to prevent life-threatening hemolysis 5
• Monitor blood pressure closely during pentamidine administration due to risk of sudden severe hypotension 8