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Early Symptomatic HIV Infection: Differential Diagnoses & Workup
Updated: Jun 9, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Other Problems to Be Considered
Retroviral syndrome
Influenza
Infectious mononucleosis
Toxoplasmosis
Rubella
Secondary syphilis
Drug reaction
Disseminated gonococcal infection
Acute viral hepatitis
Persistent generalized lymphadenopathy
CD4 cell counts greater than 200 cells/µL - Adenopathic form of Kaposi sarcoma (KS)
CD4 cell counts less than 200 cells/µL - Adenopathic form of KS, lymphoma, mycobacterial infection, toxoplasmosis, systemic fungal infection, bacillary angiomatosis
Oral lesions
CD4 cell counts greater than 200/µL - Thrush, hairy leukoplakia, aphthous ulcers, herpes simplex, herpes zoster
CD4 cell counts less than 200/µL - Thrush, hairy leukoplakia, aphthous ulcers, herpes simplex, herpes zoster, cytomegalovirus (CMV) infection, KS
Miscellaneous
All other causes of anemia
All other causes of thrombocytopenia
All other causes of meningitis
Acute inflammatory demyelinating polyneuropathy
Guillain-Barré syndrome
Lambert-Eaton syndrome
Botulism
Myasthenia gravis
Mononeuritis multiplex
Diabetes mellitus
Vitamin B-12 deficiency
Adverse effects of metronidazole (Flagyl) or dapsone
Workup
Laboratory Studies
- Patients with suspected acute human immunodeficiency virus (HIV) infection should undergo serum testing for HIV antibody and HIV antigen using HIV nucleic acid amplification, HIV p24 antigen, or PCR for viral load. Beware of false-positive HIV viral load test results (<15,000 RNA copies/mL blood).6,4
- Persistent generalized lymphadenopathy: This is diagnosed clinically. Lymph node biopsy is not indicated in patients with early-stage HIV disease unless the patient has signs and symptoms of systemic illness (eg, fever, weight loss) or enlarged, fixed, or coalescent lymph nodes. A serologic diagnosis of acute EBV or CMV mononucleosis should be considered.
- Thrush: This is diagnosed based on clinical appearance or examination of a scraping for pseudohyphal elements. Culturing is of no value because throat cultures are positive for Candida in most patients with HIV infection, even those without thrush. See Thrush for more details.
- Oral hairy leukoplakia: This is typically diagnosed based on clinical appearance. Biopsy tissue findings reveal epithelial hyperplasia with protruding hairs and minimal inflammation. EBV can be visualized with electron microscopy, immunofluorescence, or Southern blot analysis. See Hairy Leukoplakia for more details.
- Aphthous ulcers: These are diagnosed clinically. Examination of biopsy tissue reveals nonspecific inflammation and is not diagnostic. The primary role for biopsy is when aphthous ulcers are difficult to distinguish from HSV lesions. See Aphthous Stomatitis for more details.
- Herpes simplex virus: Viral culture is the criterion standard for diagnosis. Viral PCR of intralesional fluid is also highly sensitive. Direct fluorescent antigen (DFA) is also a useful and generally rapidly available test that yields good sensitivity and specificity. Tzanck preparation (ie, Giemsa stain of vesicle contents) may reveal multinucleated giant cells and intranuclear inclusions specific for HSV or VZV, but the sensitivity is low. See Herpes Simplex for more details.
- Varicella-zoster virus: Viral culture is the criterion standard for diagnosis. DFA is also a useful and generally rapidly available test with good sensitivity and specificity. Results from a Tzanck preparation (ie, Giemsa stain of vesicle contents) may reveal multinucleated giant cells and intranuclear inclusions specific for HSV or VZV, but the sensitivity is low. See Herpes Zoster for more details.
- Anemia: A thorough evaluation is essential to exclude all other causes of anemia, especially any correctable causes. In addition to the workup detailed in Anemia, measuring the serum erythropoietin (EPO) level can help distinguish between bone marrow damage (ie, normal EPO level) and inflammatory anemia (ie, low EPO level).
- Thrombocytopenia: A thorough evaluation is essential to exclude all other causes of thrombocytopenia (eg, see Thrombotic Thrombocytopenic Purpura), such as drug toxicity, lymphoma, fungal infection, and mycobacterial infection. Bone marrow examination generally reveals a normal or increased number of megakaryocytes.
- Elevated transaminases: Acute viral hepatitis A, B, and C should be excluded with appropriate serologic testing.
- Neurologic: A lumbar puncture is an important element of the evaluation in patients with HIV infection who have neurologic abnormalities. A lumbar puncture is most helpful in the diagnosis of opportunistic infections.
- Aseptic meningitis or encephalitis: Cerebrospinal fluid examination reveals lymphocytic pleocytosis, an elevated protein level, and a normal glucose level.
- Acute inflammatory demyelinating polyneuropathy: Cerebrospinal fluid examination reveals pleocytosis and increased protein levels. A peripheral nerve biopsy reveals findings of a perivascular infiltrate, suggesting an autoimmune etiology. Electromyography (EMG) findings reveal demyelination.
- Myopathy: Serial creatine kinase levels are useful for monitoring the course of HIV myopathy. EMG is a sensitive diagnostic test in patients with HIV myopathy. The most common finding after muscle biopsy is scattered myofiber degeneration with occasional inflammatory infiltrates. Other pathological findings include nemaline rod bodies, cytoplasmic bodies, and mitochondrial abnormalities.
Other Tests
- Electromyography
- The finding in acute inflammatory demyelinating polyneuropathy is demyelination.
- EMG is also useful for evaluating mononeuritis multiplex; results generally reveal multifocal axonal neuropathy.
- EMG is a sensitive test for the evaluation of HIV myopathy.
Procedures
- Acute inflammatory demyelinating polyneuropathy - Peripheral nerve biopsy
- Mononeuritis multiplex - Nerve biopsy
- Myopathy - Muscle biopsy
- Meningitis/encephalitis - Lumbar puncture and CSF analysis
Histologic Findings
- Thrush: Microscopic examination of a lesion scraping shows pseudohyphal elements.
- Oral hairy leukoplakia: Biopsy tissue reveals epithelial hyperplasia with protruding hairs and minimal inflammation. EBV can be visualized with electron microscopy, immunofluorescence, or Southern blot analysis.
- HSV and VZV: Tzanck preparation (ie, Giemsa stain of vesicle contents) may reveal multinucleated giant cells and intranuclear inclusions specific for HSV or VZV.
- Thrombocytopenia: Bone marrow examination generally reveals a normal or increased number of megakaryocytes.
- Acute inflammatory demyelinating polyneuropathy: Peripheral nerve biopsy reveals a perivascular infiltrate suggestive of an autoimmune etiology.
- Mononeuritis multiplex: Biopsy of nerve tissue reveals inflammation and vasculitis. In some cases, CMV inclusions have been found.
- Myopathy: The most common muscle biopsy finding is scattered myofiber degeneration with occasional inflammatory infiltrates. Other pathological findings include nemaline rod bodies, cytoplasmic bodies, and mitochondrial abnormalities.
More on Early Symptomatic HIV Infection |
| Overview: Early Symptomatic HIV Infection |
Differential Diagnoses & Workup: Early Symptomatic HIV Infection |
| Treatment & Medication: Early Symptomatic HIV Infection |
| Follow-up: Early Symptomatic HIV Infection |
| References |
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References
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Strategies for Management of Antiretroviral Therapy (SMART) Study Group, Emery S, Neuhaus JA, Phillips AN, Babiker A, Cohen CJ, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. Apr 15 2008;197(8):1133-44. [Medline].
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Further Reading
Keywords
early symptomatic HIV infection, acute HIV infection, acute retroviral syndrome, HIV seroconversion illness, HIV seroconversion syndrome, immune reconstitution inflammatory syndrome, human immunodeficiency virus, HIV, viral infection, immunologic impairment, immunocompromise, pre-acquired immune deficiency syndrome, pre-AIDS, thrush, oral hairy leukoplakia, herpes simplex virus, HSV, varicella-zoster virus, VZV, shingles, herpes zoster, thrombocytopenia, acute inflammatory demyelinating polyneuropathy, mononeuritis multiplex, myopathy, persistent generalized lymphadenopathy, PGL, oral lesions, anemia, aseptic meningitis, aphthous ulcers
Differential Diagnoses & Workup: Early Symptomatic HIV Infection