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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ujjwal Rastogi, MBBS, Ammu Susheela, M.D. [2]

Overview

Acute HIV infection may be asymptomatic or may cause a mononucleosis-like syndrome. It should be differentiated from similar diseases that cause fever, fatigue, sore throat, myalgia, and lymphadenopathy such as acute toxoplasmosis, acute CMV/EBV infections, and acute viral hepatitis. On the other hand, AIDS should be considered in all patients presenting with symptoms of immunodeficiency or opportunistic infections. It should be distinguished from various medical states that cause immunosuppression including common variable immune deficiency (CVID), chemotherapy treatment, steroid therapy, and severe malnutrition.[1]

Differential Diagnosis

Acute HIV

Disorder Disease Definition
Burkitt's lymphoma Burkitt's lymphoma (or "Burkitt's tumor", or "Malignant lymphoma, Burkitt's type") is a cancer of the lymphatic system (in particular, B lymphocytes). It is associated with the Epstein-Barr virus, also the cause of infectious mononucleosis as well as other cancers such as nasopharyngeal carcinoma and thymic carcinoma.
Influenza Influenza is an infectious disease caused by RNA viruses of the biological family Orthomyxoviridae. The common symptoms of influenza infection are fever, sore throat, muscle pains, severe headache, coughing, weakness and general discomfort. In more serious cases, influenza causes pneumonia, which can be fatal, particularly in young children and the elderly
Streptococcal pharyngitis Streptococcal pharyngitis is a form of group A streptococcal infection that affects the pharynx, and possibly the larynx and tonsils and presents as sore throat. Similar symptoms may be seen with acute HIV syndrome
Viral gastroenteritis Gastroenteritis is the inflammation of the stomach and the small and large intestines. Viral gastroenteritis is an infection caused by a variety of viruses or bacteria that presents with abdominal pain, vomiting, and/or diarrhea.
Viral upper respiratory tract infection A variety of acute viral infections of the upper respiratory tract can cause symptoms similar to the acute HIV syndrome including fever, myalgia, pharyngitis, and malaise.
Acute viral hepatitis Acute viral inflammation of the liver can cause loss of appetite, malaise, jaundice and other constitutional syndromes similar to acute HIV.
Primary herpes simplex infection Herpes simplex is a viral infection that causes that can produce various symptoms depending on the sites of infection. Oral herpes can cause cold sores in mouth and is the most common for of Infection. It can have active and latent phases. Although Herpes can occur as an opportunistic infection in the immunocompromised state of AIDS infection, primary herpes simplex infection can be a differential diagnosis of AIDS.
Secondary syphilis After 4-10 weeks of primary syphilis , secondary syphilis can occur affecting skin, mucous membrane and lymph nodes. They can present with fever, malaise, sore throat, weight loss, headache , hair loss.
Acute CMV infection Human cytomegalovirus is a genus of viruses belonging to the viral family herpesviridae. CMV infection is typically unnoticed in healthy people, but can be life-threatening for immunocompromised patients, particularly those with AIDS, organ transplant recipients, and newborns. CMV infections may present with a mononucleosis-like syndrome seen in patients with acute HIV syndrome.
Acute toxoplasmosis A parasitic disease caused by ingestion of cat feces, affect all organs and particularly dangerous in pregnant woman. Toxoplasma infections may also present with a mononucleosis-like syndrome seen in patients with acute HIV syndrome.
Brucellosis Brucellosis is a Zoonotic disease caused by bacteria of the genus Brucella. It is primarily a disease of domestic animals (goats, pigs, cattle, dogs, etc) and humans and has a worldwide distribution, mostly now in developing countries.
Disseminated goncoccemia Gonococcemia is a condition characterized by a hemorrhagic vesiculopustular eruption, bouts of fever, and arthralgia or arthritis.
Measles Measles is a disease caused by the measles virus belonging to the genus Morbillivirus. It is transmitted into by contact and aerosols. Symptoms include the appearance of a diffuse maculopapular rash along with fever, cough, coryza, conjunctivitis, malaise, and fatigue.
Meningitis/Encephalitis Encephalitis is an acute inflammation of the brain, commonly caused by a viral or bacterial infections.
Primary immunodeficiencies Other immunodeficiency syndromes can produce similar symptoms of AIDS. These include primary congenital immunodeficiencies, secondary immunodeficiencies particularly iatrogenic and neoplastic in nature.
Malaria Malaria is a vector-borne infectious disease caused by protozoan parasites. Malaria is one of the most common infectious diseases and an enormous public-health problem. The disease is caused by protozoan parasites of the genus Plasmodium. The most serious forms of the disease are caused by Plasmodium falciparum and Plasmodium vivax, but other related species (Plasmodium ovale,Plasmodium malariae, and sometimes Plasmodium knowlesi) can also infect humans. Malaria may present with cyclical fevers, myalgia, and other flu-like syndromes that may be observed in patients with acute HIV syndrome.
Typhoid Typhoid fever, also known as enteric fever, is an illness caused by the bacterium Salmonella enterica serovar typhi. Common worldwide, it is transmitted by the fecal-oral route. Symptoms include adbominal pain, fever, malaise, headache, and bradycardia.
Rubella Rubella is a common childhood infection usually with minimal systemic manifestations. Transplacental infection is a particular concern given the increased risk of congenital defects.

AIDS

The table shown bellow describes the most common conditions that should be differentiated from AIDS as they all cause immunodeficiency and patients with those diseases are prone to opportunistic infections.

Condition Description
Cancer [2] Most hematological cancers and some solid cancers are associated with acquired immunodeficiency and should be ruled out. These include leukemias, lymphomas, plasmacytomas, melanoma, and central nervous system tumors.
Chemotherapy [3][4] Immunosuppresive drugs will used in the treatment of cancer, rheumatic diseases, and following organ transplants diminish the immune response by interfering with nucleic acid synthesis and decreasing the subsets of B and T cells. Examples include methotrexate, azathioprine, mercaptopurine, fluorouracil, and dactinomycin.
Steroid Therapy Glucocorticoids act by inhibiting genes that code for the cytokines and humoral activity, which leads to immunosuppresion when used for long periods of time. Opportunistic infections such as candidiasis or herpes zoster may be seen in these patients.
Malnutrition Patients with malnutrition will have a weakened immune system due to the lack of essential nutrients to create new immune cells and are prone to infections that are also seen in AIDS. Special populations are prone to malnutrition, such as kids (marasmus, kwashiorkor) and the elderly.
Common Variable Immunodeficiency (CVID) Patients with CVID are usually between 20 and 40 years old and their cellular and humoral immune system are affected. CVID should be ruled out if the HIV test is negative and the patient presents with immunodeficiency.
Other Congenital Immunodeficiencies These include: Severe Combined Immunodeficiency (SCID), X-linked agammaglobulinemia, DiGeorge syndrome, and Wiskott-Aldrich syndrome.

AIDS must be differentiated from other causes of rash and arthritis[5][6][7]

Disease Findings
Nongonococcal septic arthritis
  • Presents with an acute onset of joint swelling and pain (usually monoarticular)
  • Culture of joint fluid reveals organisms
Acute rheumatic fever
  • Presents with polyarthritis and rash (rare presentation) in young adults. Microbiologic or serologic evidence of a recent streptococcal infection confirm the diagnosis.
  • Poststreptococcal arthritis have a rapid response to salicylates or other antiinflammatory drugs.
Syphilis
  • Presents with acute secondary syphilis usually presents with generalized, pustular lesions at the palms and soles with generalized lymphadenopathy
  • Rapid plasma reagin (RPR), Venereal Disease Research Laboratory (VDRL) and Fluorescent treponemal antibody absorption (FTA-ABS) tests confirm the presence of the causative agent.
Reactive arthritis (Reiter syndrome)
  • Musculoskeletal manifestation include arthritis, tenosynovitis, dactylitis, and low back pain.
  • Extraarticular manifestation include conjunctivitis, urethritis, and genital and oral lesions.
  • Reactive arthritis is a clinical diagnosis based upon the pattern of findings and there is no definitive diagnostic test
Hepatitis B virus (HBV) infection
  • Presents with fever, chills, polyarthritis, tenosynovitis, and urticarial rash
  • Synovial fluid analysis usually shows noninflammatory fluid
  • Elevated serum aminotransaminases and evidence of acute HBV infection on serologic testing confirm the presence of the HBV.
Herpes simplex virus (HSV)
  • Genital and extragenital lesions can mimic the skin lesions that occur in disseminated gonococcal infection
  • Viral culture, polymerase chain reaction (PCR), and direct fluorescence antibody confirm the presence of the causative agent.
HIV infection
  • Present with generalized rash with mucus membrane involvement, fever, chills, and arthralgia. Joint effusions are uncommon
Gout and other crystal-induced arthritis
  • Presents with acute monoarthritis with fever and chills
  • Synovial fluid analysis confirm the diagnosis.
Lyme disease
  • Present with erythema chronicum migrans rash and monoarthritis as a later presentation.
  • Clinical characteristics of the rash and and serologic testing confirm the diagnosis.

Other Differentials

AIDS should be differentiated from other conditions presenting with fever, fatigue, weight loss, arthralgia, myalgia, rash and soft tissue swelling. The differentials include the following:[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]

Category of Disease Diseases Signs and symptoms Laboratory findings
Fever Fatigue Arthralgia Myalgia Soft tissue swelling/serositis Skin rash Weight loss Dyspnea Sore throat Lymphadenopathy Complete blood count (CBC) Liver function tests (LFTs)

Inflammatory markers

Autoantibodies

Diagnostic tests

Erythrocyte sedimentation rate (ESR) C- reactive protein (CRP) Anti-nuclear antibodies (ANA) Rheumatoid factor (RF) Anti- glomerular basement membrane (anti-GBM) Anti-dsDNA Anti-Jo1/ Anti Mi2 ANCA

Infections

 HIV + + + + +/- - + +/- + /- + - - - - - -
 Herpesviridae + + + + + - - +/- + - - - - - - -
 Measles + + + + - - - + + - - - - - - -
 Viral hepatitis + + - +/- - - +/- - - +/- - - - - - -
 Parvovirus B19 + + + +/- -
  • Slapped cheek rash
- - - + - - - - - -
Infective endocarditis + + + +/- - +/- + - + - - - - - - - Blood cultures, ultrasonography
Borreliosis, Brucellosis, Yersiniosis + + + + - - - - + - - - - - - Serology, PCR
Syphilis and Jarisch-Herxheimer reaction + + + + - - - + +
  • ALT (Uncommon)
  • AST (Uncommon)
- - - - - - Serology, PCR
Toxoplasmosis + + - + - - - + + - - - - - - Serology, PCR

Neoplasia

Malignant lymphoma + + - +/- +/- + + - + - - - - - - CT, PET/CT, Bone marrow examination, lymph node biopsy
Multicentric Castleman disease + + - - + - + + - + - - - - - - - Lymph node biopsy
Angioimmunoblastic T cell lymphoma + + - - - + - - + - - - - - - Lymph node biopsy

Drug hypersensitivity

Drug reaction with eosinophilia and systemic symptoms + + + + +/- - + - - - - - - - - - Eosinophil count, skin biopsy

Autoimmune conditions

Systemic lupus erythematosus + + + +/- + + + - +/- + + - + - - Antinuclear autoantibodies
Inflammatory myositis + + - + (weakness > pain) -
  • Macular red rash over the back of the fingers, elbows or knees (Grotton's sign)
  • Macular purpish or reddish rash on the upper chest or back  (Shawl-like, heliotrope rash)
- - - +/- - +/- +/- - - + - Idem, muscle biopsy
Rheumatoid arthritis + + + - + - + - + - +/- +/- - - - - Anti-citrullinated peptids autoantibodies, rheumatoid factor
Systemic vasculitides + + + - + - +/- - +/- - - - +/- - - + ANCA, tissue biopsy, arteriography
Familial Mediterranean fever + + + + + + + (due to pain) - +/- - - - - - - - Familial history, MEFV gene analysis
Mevalonate kinase deficiency + + + + - + - + + - - - - - - - Urinary mevalonic acid, mevalonate kinase analysis
Reactive arthritis + + + - - - + (Aortic insufficiency) - + - - - - - - - HLA B27, magnetic resonance imaging

Miscellaneous

Sarcoidosis + + + - + + + - +
  • Normal ALT, AST
  • ALP ↑ (infiltrative pattern)
- - - - - -
  • Lymph node/Lung biopsy
  • ACE levels
  • FDG-PET

References

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