Pediatric HIV Infection Clinical Presentation

Updated: Sep 13, 2017
  • Author: Delia M Rivera, MD; Chief Editor: Russell W Steele, MD  more...
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Presentation

History

Ideally, the diagnosis of HIV in a child is made through perinatal testing. The Centers for Disease Control and Prevention (CDC) has issued guidelines for recommended testing and counseling for all pregnant women; however, many women, especially in developing countries and in poorer areas of the developed world, do not have access to or do not avail themselves of the resources available. Thus, for example, the diagnosis of HIV infection may follow an investigation of a prolonged or unusual presentation of an infection or a malignancy.

Some studies suggest that children vertically infected with HIV become symptomatic from the neonatal period up to age 8 years and that 57% of this group have associated disease within the first year.

Children infected as a result of sexual abuse or drug use may not present with known HIV infection.

Immunodeficiency should be suspected in individuals with recurrent bacterial infections (especially invasive infections, eg, bacteremia, meningitis, and pneumonia) and in those with unusual infections, such as those caused by the Mycobacterium avium-intracellulare complex (MAC).

Children with HIV infection often present with the common bacterial infections of childhood (eg, otitis media, sinusitis, pneumonia). These can be more frequent and more severe than similar infections in immunologically healthy children. Recurrent fungal infections, such as candidiasis (thrush), that do not respond to standard antifungal agents suggest lymphocytic dysfunction.

Recurrent or unusually severe viral infections, such as recurrent or disseminated herpes simplex or zoster infection or cytomegalovirus (CMV) retinitis, are seen with moderate-to-severe cellular immune deficiency.

Growth

Growth failure, failure to thrive, or wasting in a child may indicate HIV infection if other common metabolic and endocrine disorders do not appear to be the etiologies. Growth failure, failure to thrive, or wasting in a patient with HIV infection may signify disease progression or underlying malnutrition.

Development

Failure to attain typical milestones suggests a developmental delay. Such delays, particularly impairment in the development of expressive language, may indicate HIV encephalopathy. The loss of previously attained milestones may signify a CNS insult due to progressive HIV encephalopathy or opportunistic infection.

In older children, behavioral abnormalities (eg, loss of concentration and memory) may indicate HIV encephalopathy.

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Physical Examination

A high percentage of oral disease has been seen in children infected with HIV, and oral manifestations are often early indicators of infection. Numerous mucocutaneous disorders have been reported in children infected with HIV. As the CD4+ count decreases, an increase in the number and severity of skin manifestations can be expected. Dermatologic manifestations occur more frequently in children with advanced HIV disease; many tend to improve after antiretroviral therapy is initiated.

The most common oral disease and mucocutaneous presentation of HIV infection is candidiasis caused by Candida albicans. Both the pseudomembranous variant and the atrophic oral variant are most common.

Pseudomembranous candidiasis manifests as creamy white-to-yellow oral plaques, commonly referred to as thrush. Atrophic candidiasis manifests as distinct areas of erythema with the loss of tongue papillae if the tongue is affected. Hyperplastic candidiasis (with both erythematous and white mucosal coloration symmetrically distributed) and angular cheilitis are 2 additional clinical variants of candidiasis.

The usual symptoms in children with candidal esophagitis are odynophagia, dysphagia, and retrosternal pain. [17] These symptoms may contribute to the already-compromised nutritional status of the child.

An inflammatory, destructive, and necrotic process characterizes candidal periodontal disease in the gingival mucosa and the underlying connective tissue.

Although C albicans is the most commonly identified Candida species, C dubliniensis has garnered notice as a cause of oral infection that is seen, for the most part, only in patients who are HIV positive. [18] Other Candida species implicated in HIV-related candidiasis are C glabrata and C tropicalis.

Candidiasis may manifest as an unresponsive or recurrent diaper rash or as a chronic paronychia and onychomycosis. In Candida -associated diaper dermatitis, the area covered by the diaper is usually inflamed and erythematous, with satellite lesions extending beyond the central area of involvement. Involvement of other intertriginous areas, including neck folds and axillary regions, has also been reported.

Candidal involvement of the proximal nailfolds causes severe paronychia and nail dystrophy. Candidal onychomycosis results in yellow-brown thickened nail plates.

Linear gingival erythema and median rhomboid glossitis have also been found, especially in children with a low CD4+ cell count.

Children infected with HIV have a higher rate of dental caries in the primary teeth but a diminished prevalence in the permanent teeth, a finding attributed to the greater number of primary teeth and the delayed eruption of the permanent teeth in these patients. HIV-infected children should be screened and considered at high risk for dental caries, usually secondary to chronic medication use. [19, 20]

Oral hairy leukoplakia, which is associated with Epstein-Barr virus, is usually rare in US children, but it has been reported in children as the second most common oral presentation after candidiasis in some Asian countries. Results from a 2006 Brazilian study suggest that oral hairy leukoplakia may be more common than previously believed; 16.7% of patients demonstrated subclinical, cytological disease, although only 1.7% of children had clinically visible disease. [21]

Herpes simplex virus infections, parotid enlargement, and recurrent aphthous ulcers are also common oral manifestations.

Dermatophytosis manifesting as an aggressive tinea capitis, corporis, versicolor, or onychomycosis may be challenging to treat. As in adults, Trichophyton rubrum infection in the form of proximal, white, subungual onychomycosis is categorized as a typical nail manifestation of HIV disease.

Deep fungal infections are not commonly seen in children who are HIV positive. Cryptococcosis, sporotrichosis, and histoplasmosis have been reported as either localized or disseminated variants. Molluscumlike Cryptococcus papules have been identified in some patients.

Herpetic infection with herpes simplex virus (HSV) may take the form of herpes labialis; gingivostomatitis; esophagitis; or as chronic erosive, vesicular, and vegetating skin lesions. The involved areas of the lips, mouth, tongue, and esophagus are ulcerated, which may result in difficulty with oral nutritional intake.

Skin lesions usually manifest as chronic erosions, which may have grouped vesicles. The fingers are a frequent site of infection. Pyoderma gangrenosum and ecthyma gangrenosum may be in the differential diagnosis of cutaneous herpetic infections.

Recurrent or persistent varicella-zoster infection is strongly linked with the CD4+ count. Scarring can occur from a severe outbreak, in which lesions may be hyperkeratotic and/or hemorrhagic and involve more than 1 dermatome.

Because herpes zoster is usually not seen in children who are immunocompetent, an evaluation for HIV infection should be undertaken in a child with this diagnosis. Children should be evaluated for evidence of dissemination because disastrous sequelae, such as encephalitis, intracranial thrombosis, fulminant hepatitis, disseminated intravascular coagulation, pneumonitis, and retinal necrosis, have been reported in patients with dissemination.

Human papillomavirus infection, which may mimic the tinea versicolor–like rash in epidermodysplasia verruciformis, is noted. Large areas of flat warts most commonly occur on the forehead, the temples, the neck, and the upper body. Unusually large treatment-resistant condylomata are reported in children who are HIV positive.

Widespread molluscum contagiosum can occur in pediatric AIDS patients. Molluscum contagiosum may manifest as a diffuse eruption of umbilicated papules involving areas (eg, face) usually not affected in patients who are immunocompetent. Molluscum lesions tend to be more persistent in patients with HIV infection. Some lesions are large and may be confused with Cryptococcus neoformans lesions. Molluscum tends to improve with antiretroviral therapy.

Recurrent bacterial infections are seen in children who are HIV positive because of the abnormal B-cell response and consequent defective humoral immunity. A variety of bacterial infections occurs, the most common of which is caused by Staphylococcus aureus. As the CD4+ count decreases, invasive bacterial infections, including sepsis and pneumonia, may occur.

Sepsis, otitis media, impetigo, cellulitis, and furunculosis have been reported. Although the infections may initially manifest in a manner similar to that in a child who is not immunocompromised, widespread and persistent infection should prompt consideration of HIV status. Acral lesions should be sought if sepsis is a concern because a pustule on the sole may be the first sign of sepsis.

Atypical presentations, such as plaquelike staphylococcal folliculitis, are also reported.

Rare conditions, such as ecthyma gangrenosum as a result of infection by Pseudomonas aeruginosa, are also noted. In this disorder, hemorrhagic necrotic bullae that eventually form a black eschar manifest primarily on the extremities and the gluteal and perineal regions.

Bacillary angiomatosis caused by Bartonella henselae and Bartonella quintana is rare in children but has been reported. [22] Bacillary angiomatosis is considered by some to be an AIDS-defining opportunistic infection, typically seen with a CD4+ count less than 200 cells/μL. Clinically and histologically, the lesions often resemble pyogenic granulomas and Kaposi sarcoma. They often begin as pinpoint papules, which enlarge to become red nodules and usually involve the face or the upper torso. In addition to the cutaneous findings, these patients may have lymphadenopathy, abdominal symptoms, anemia, and an elevated alkaline phosphatase level.

Mycobacterial infections caused by Mycobacterium tuberculosis and M avium complex are increasing in incidence in children who are HIV positive. These children are usually extremely sick. Usually, pulmonary disease is present, but extrapulmonary findings can also occur. Acute pustular eruptions, widespread keratotic papules with hyperkeratotic palms and soles, tuberculous lymphadenitis, purple necrotic lesions, and ulcerations have been reported in HIV-associated mycobacterial infections.

M haemophilum often causes disseminated infection in patients with AIDS. Diffuse swelling and induration of the periarticular soft tissue and nodular formation are reported in patients infected with M haemophilum.

Pneumocystis jiroveci (formerly P carinii) pneumonia (PCP) is the primary AIDS-defining illness and occurs in 7-20% of patients who have not been administered prophylaxis and are younger than 1 year. Most commonly, PCP manifests as cough, dyspnea, tachypnea, and fever. The incidence of PCP is declining in areas where AIDS medications are available, but it continues to shorten life expectancy in areas in which access to antiretrovirals is limited.

Scabies in children infected with HIV may progress from a widespread pruritic papular eruption to a crusted variant as the CD4+ count decreases. This crusted (Norwegian) variant is characterized by an extremely high mite count and thus is very contagious. Secondary bacterial infection may complicate crusted scabies.

In regions of the world where measles vaccination is not routinely administered and where HIV is endemic, the potential for serious measles infection exists. [7, 23] Measles typically manifests with an erythematous macular eruption of the trunk with caudal spread. Koplik spots (small blue-white dots surrounded by erythematous rings on the buccal mucosa) are the most common oral manifestation. In children who are immunocompromised, measles may manifest without skin involvement but with more severe complications.

Death from pneumonitis and encephalitis has been reported in African children with both HIV infection and measles.

Noma (cancrum oris) is a necrotic disease of tissues of the mouth. [24] This disease quickly spreads to surrounding bone and soft tissue and is often associated with immunodeficient states, such as AIDS. Noma predominately occurs in young children from sub-Saharan Africa and is often associated with measles.

Seborrheic dermatitis may be a manifestation of HIV in children who present outside of the usual neonatal and adolescent timeframes or who present with generalized disease. An association between Pityrosporum orbiculare growth in the presence of waning CD4+ cells and Langerhans cells has been postulated.

The eczematous periorofacial eruption of acrodermatitis enteropathica caused by nutritional deficiency of zinc, secondary to diarrhea-induced malabsorption, has been reported. Other vitamin deficiencies can also be expected because of poor oral intake or diarrhea.

Metabolic abnormalities have been reported in association with pediatric HIV disease. Lipodystrophy associated with insulin resistance and dyslipidemia occurs in children who are HIV positive (similar to adults who are HIV positive) and may be attributed to highly active antiretroviral therapy, although individual variations may make certain children more susceptible. [25] See also HIV Lipodystrophy.

Variations in presentation include peripheral lipoatrophy, truncal lipohypertrophy, and combined versions of these presentations. A more severe presentation occurs at puberty. Thyroid abnormalities with hypothyroidism have also occurred in children infected perinatally. [26]

A variety of skin conditions, including exaggerated eczema, psoriasis, drug eruptions (including morbilliform eruptions and Stevens-Johnson syndrome), intense reactions to arthropod bites, [27] alopecia, and trichomegaly, have been reported in children who are HIV positive.

Children with HIV infection are at risk for child abuse because of family stressors; therefore, unusual skin lesions should be evaluated for potential signs of exogenous injury.

A higher incidence of neoplasia is noted in children with HIV infection than in noninfected children. [28] B-cell lymphoproliferative diseases, including non-Hodgkin lymphoma, Burkitt lymphoma, and smooth muscle tumors, have been identified.

The prevalence of HIV-associated malignancies has been reported to be as high as 2%. A 2005 evaluation of 2969 pediatric patients with AIDS in the United States from 1993-2003 revealed that the incidence of malignancy is 1.56 cases per 1000 person-years, a number lower than in European counterparts but significantly higher than in noninfected children. [29]

Kaposi sarcoma is unusual in children; however, an African study has shown the childhood incidence of Kaposi sarcoma has risen more than 40-fold since the advent of the AIDS epidemic. [30] Previously thought to only occur in males, it has been reported in both males and females born to mothers who are infected with HIV in high-risk groups for Kaposi sarcoma or in children infected postnatally by blood products. The most common sites of AIDS-related Kaposi sarcoma in children are the orofacial and the inguinal or genital regions. [31]

Few physical findings are specific to HIV infection, and many physical findings are caused by opportunistic infections. Lymphadenopathy, hepatomegaly, and splenomegaly are fairly common in HIV infection. Other findings may include those discussed below.

Anthropometric findings

Monitoring the patient's growth is one of the most important parts of the pediatric physical examination. Anthropometric measurements should be obtained at each visit.

Delayed growth in the head circumference is correlated with the development of underlying encephalopathy. However, normal head growth does not help in ruling out encephalopathy, and many patients with a normal head circumference may have radiographic or psychometric findings consistent with encephalopathy.

Fat redistribution syndrome in association with lipid abnormalities and insulin resistance is being described in HIV-infected children and adults. Presentations vary (eg, central adiposity vs peripheral fat wasting) and depend on factors such as race and age. Body habitus is altered because of lipoatrophy, lipohypertrophy, or both.

Diverse diagnostic criteria have been used. Anthropometric measurements, such as skin-fold thickness and the waist-to-hip ratio, are useful to monitor the progression of changes. Technically sophisticated tools include bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DEXA), CT, and MRI.

Head, eyes, ears, nose, and throat (HEENT) findings

Parotid enlargement is observed in 30% of children with category C disease (see Staging) and in 15% of children with disease in other categories.

Tonsillar hypertrophy may be observed. Aphthous ulcers may be observed.

Thrush in the oral cavity and posterior pharynx is observed in approximately 30% of HIV-infected children. In children with AIDS, the prevalence of thrush is correlated with a low CD4+ count. Thrush in the posterior pharynx may signify candidal esophagitis, especially in patients with feeding difficulties or retrosternal pain.

CMV retinitis occurs in 3.4% of children with CD4+ counts of less than 50/mL.

Cardiac, pulmonary, and abdominal findings

Cardiomyopathy may be present. Congestive heart failure may be present.

Lung examination is important, and good documentation of findings is required at each visit. Chronic lung disease may produce baseline findings of crackles and decreased regional breath sounds.

Changes in the lung findings are important to note because pneumonia is common in children with HIV infection. Pneumonia may not be obvious during the examination, and many children have few symptoms. For example, Mycoplasma infection may not cause a high temperature, and Pneumocystis jiroveci infection may cause only tachypnea, fever, and hypoxemia.

Changing findings at lung examination may also signify worsening of chronic lung disease, lymphoid interstitial pneumonitis, or tuberculosis.

Hepatomegaly is observed in 45% of HIV-infected children without AIDS and in 70% of those with AIDS. Splenomegaly is observed in about 35% of children with HIV infection.

Lymphatic findings

Generalized cervical, axillary, or inguinal lymphadenopathy is common and may be the first sign of initial infection during the asymptomatic phase of the disease. Generalized lymphadenopathy may not be present with well-controlled disease or end-stage AIDS. New shotty nodes may indicate that the disease has again progressed and that treatment failure has occurred.

A single large node may indicate lymphoma, and it may need to be examined with biopsy.

Neurologic findings

Motor delay, hypotonia, hypertonia, and/or pyramidal-tract signs may indicate progressive HIV encephalopathy or opportunistic infection of the CNS.

Spastic diplegia and oral motor dysfunction are early signs of encephalopathy.

Acquired microcephaly with accompanying cerebral atrophy is a poor prognostic sign.

Subacute combined degeneration of the spinal cord with higher cortical dysfunction occurs in vitamin B-12 deficiency.

Ischemic and hemorrhagic strokes can occur in children with AIDS, but they seem to be related to infection or other mechanisms other than atherosclerosis or hypercoagulable states, as in the adult HIV-infected population.

Skin findings

HIV dermatitis causes an erythematous papular rash and is observed in about 25% of children with HIV infection.

Vesicular lesions in a unilateral dermatomal distribution or in the oral, genital, or anal area may represent reactivation of herpes zoster.

Erythematous candidal dermatitis that does not respond to standard therapy may be present.

Bleeding or bruising of the mucous membranes and skin may be observed in children with HIV and immune thrombocytopenic purpura, although this is uncommon.

Extremity findings

Digital clubbing may be observed as a result of chronic lung disease.

Nonpitting edema may result from hypoalbuminemia caused by HIV nephropathy or malnutrition. Pitting edema may develop as a result of congestive heart failure.

Opportunistic infections

PCP is the most common opportunistic infection in children with vertically transmitted HIV infection unless antibiotic prophylaxis is used. Without prophylaxis, PCP commonly occurs in infants aged 3 months. Without prophylactic suppression, infection may develop in infants younger than 1 year regardless of their baseline CD4+ count because the rapid progression of immunosuppression may precipitate a sharp decrease in their CD4+ counts.

PCP typically occurs in children with moderate immune suppression; this warrants category C classification.

Upon examination, fever and tachypnea are usually the presenting symptoms. Chest radiographs may or may not show diffuse interstitial pulmonary infiltrates. Lung examination may or may not reveal rales. The diagnosis is confirmed by detecting PCP antigen in a sputum or, preferably, in a specimen obtained during bronchoscopic lavage.

Systemic complications

Dysrhythmias, hemodynamic abnormalities, and cardiomyopathy develop in about 20% and 5% of HIV-infected children with AIDS and those without AIDS, respectively. Congestive heart failure is a late manifestation of HIV infection. Children must be treated symptomatically with sodium restriction, diuretics, digitalis glycosides, and angiotensin converting–enzyme inhibitor (ACEI) therapy. Progressive changes in cardiac structure are correlated with disease progression.

Chronic diarrhea develops in approximately 15% of children with HIV infection. Infectious agents may cause diarrhea. MAC and Cryptosporidium species are not uncommon causes of diarrhea in children with low CD4+ counts.

Stool examination and cultures for bacteria, fungi, viruses, parasites, and acid-fast organisms should be performed every day for at least 3 days, with special instructions for detecting Cryptosporidium,Isospora, and microsporidia organisms. Clostridium difficile tests should be requested if patients currently or recently received antimicrobial therapy.

Bile-acid malabsorption, but not bacterial overgrowth, appears to contribute to chronic diarrhea of HIV. Cholestyramine 4-8 g given 3 times a day may substantially slow diarrhea in some patients.

Pancreatitis can develop from medication, ascending infection, or the HIV infection itself. Amylase and lipase levels should be monitored in patients at risk for pancreatitis with abdominal complaints.

Abdominal pain with associated diarrhea, hepatosplenomegaly, intestinal lymphadenopathy, fever, or anemia is common in disseminated MAC infection.

In adults, wasting syndrome is common with advanced disease. Although older children with advanced disease may have wasting syndrome, young children have growth failure even without advanced disease. Undiagnosed HIV infection may present in patients with a diagnosis of failure to thrive.

Nephropathy

In approximately 15% and 5% of HIV-infected children with AIDS and those without AIDS, respectively, the disease progresses to HIV nephropathy. HIV nephropathy is more common in African American children than in others.

Proteinuria and hyponatremia with elevation in BUN and creatinine levels and a slight increase in blood pressure develop early and are not uncommon.

Renal biopsy most often reveals focal segmental glomerulosclerosis or, sometimes, mesangial hyperplasia. Necrotizing glomerulonephritis and minimal histologic changes also are observed.

Angiotensin-converting enzyme inhibitors appear to have kidney-sparing effects and are being studied.

Symptomatic treatment with fluid restriction, a low-salt diet, and diuretics may be needed in cases of frank nephrosis.

Non-HIV nephropathy may develop, especially in children who are treated with repeat courses of nephrotoxic medications. Some children have chronic renal failure with electrolyte wasting. Electrolyte levels should be monitored closely, and patients should receive appropriate supplementation.

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