HIV AIDS differential diagnosis

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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.

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	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	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

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:

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	+	+	+	+	+/-	-	+	+/-	+ /-	+	Leukopenia Anemia Thrombocytopenia	ALT↑ AST↑	↑	↑	-	-	-	-	-	-
	Herpesviridae	+	+	+	+	+	Papular or vesicular Erythematous base Painful	-	-	+/-	+	Leukocytosis	-	↑	↑	-	-	-	-	-	-
	Measles	+	+	+	+	-	3-5 days after fever Erythematous maculopapular rash starts on face spreads to trunk and extremities (centrifugal)	-	-	+	+	Leukocytosis	-	↑	↑	-	-	-	-	-	-
	Viral hepatitis	+	+	-	+/-	-	-	+/-	-	-	+/-	Leukocytosis	ALT↑ AST↑	↑	↑	-	-	-	-	-	-
	Parvovirus B19	+	+	+	+/-	-	Slapped cheek rash	-	-	-	+	Leukopenia Aplastic anemia (low reticulocyte count) Thrombocytopenia	ALT↑ AST↑	↑	↑	-	-	-	-	-	-
	Infective endocarditis	+	+	+	+/-	-	Purpuric	+/-	+	-	+	Leukocytosis	-	↑	↑	-	-	-	-	-	-	Blood cultures, ultrasonography
	Borreliosis, Brucellosis, Yersiniosis	+	+	+	+	-	Target rash (Borrelia) Diffuse maculopapular (Brucellosis) Erythema nodosum (Yersiniosis)	-	-	-	+	Leukocytosis	ALT↑ AST↑	↑	↑	-	-	-	-	-	-	Serology, PCR
	Syphilis and Jarisch-Herxheimer reaction	+	+	+	+	-	Non-pruritic Macular On palms and soles Round Seen in secondary syphilis Penile ulceration (painless)	-	-	+	+	Leukocytosis	ALT↑ (Uncommon) AST↑ (Uncommon)	↑	↑	-	-	-	-	-	-	Serology, PCR
	Toxoplasmosis	+	+	-	+	-	Maculopapular Palms and soles	-	-	+	+	Leukocytosis (eosinophilia)				-	-	-	-	-	-	Serology, PCR
Neoplasia	Malignant lymphoma	+	+	-	+/-	+/-	Purplish scaly rash in cases of cutaneous lymphoma	+	+	-	+	Anemia of chronic disease	In case of liver metastasis (Non-Hodgkin lymphoma): ALT↑ AST↑	↑	↑	-	-	-	-	-	-	CT, PET/CT, Bone marrow examination, lymph node biopsy
	Multicentric Castleman disease	+	+	-	-	+	-	+	+	-	+	Anemia Thrombocytopenia	-	↑	↑	-	-	-	-	-	-	Lymph node biopsy
	Angioimmunoblastic T cell lymphoma	+	+	-	-	-	Maculopapular eruption on the trunk mimicking toxic erythema	+	-	-	+	Lymphocytosis	ALT↑ AST↑	↑	↑	-	-	-	-	-	-	Lymph node biopsy
Drug hypersensitivity	Drug reaction with eosinophilia and systemic symptoms	+	+	+	+	+/-	Utricaria (Immediate type) Maculopapular (Delayed type)	-	+	-	-	Leukocytosis (eosinophilia)	-	↑	↑	-	-	-	-	-	-	Eosinophil count, skin biopsy
Autoimmune conditions	Systemic lupus erythematosus	+	+	+	+/-	+	Butter-fly shaped erythematous malar rash that spares the nasolabial folds Coin-shaped erythematous rash on extremities or trunk	+	+	-	+/-	Leukopenia Hemolytic anemia Thrombocytopenia	ALT↑ AST↑	↑	↑	+	+	-	+	-	-	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)	-	-	-	+/-	Leukocytosis	-	↑	↑	+/-	+/-	-	-	+	-	Idem, muscle biopsy
	Rheumatoid arthritis	+	+	+	-	+	Purpura Ulcers	-	+	-	+	Anemia of chronic disease Neutropenia (Felty's syndrome)	-	↑	↑	+/-	+/-	-	-	-	-	Anti-citrullinated peptids autoantibodies, rheumatoid factor
	Systemic vasculitides	+	+	+	-	+	Nasopharyngeal ulceration (Wegner's granulomatosis) Erythematous rash on palms and soles (Kawasaki disease)	-	+/-	-	+/-	Leukocytosis	-	↑	↑	-	-	+/-	-	-	+	ANCA, tissue biopsy, arteriography
	Familial Mediterranean fever	+	+	+	+	+	Red rash on lower extremities (ankles and knees)	+	+ (due to pain)	-	+/-	Leukocytosis (during acute flares)	-	↑	↑	-	-	-	-	-	-	Familial history, MEFV gene analysis
	Mevalonate kinase deficiency	+	+	+	+	-	Maculopapular rash Aphthous ulcers (or stomatitis)	+	-	+	+	Leukocytosis (during acute flares)	-	↑	↑	-	-	-	-	-	-	Urinary mevalonic acid, mevalonate kinase analysis
	Reactive arthritis	+	+	+	-	-	Keratoderma blennorrhagica (palms, soles, scrotum) Circinate balanitis (penile)	-	+ (Aortic insufficiency)	-	+	Leukocytosis	-	↑	↑	-	-	-	-	-	-	HLA B27, magnetic resonance imaging
Miscellaneous	Sarcoidosis	+	+	+	-	+	Waxy skin plaques Violaceous facial lesions Erythema nodosum	+	+	-	+	Lymphopenia Eosinophilia	Normal ALT, AST ALP ↑ (infiltrative pattern)	↑	↑	-	-	-	-	-	-	Lymph node/Lung biopsy ACE levels FDG-PET