Differentials
Tuberculosis
SIGNS / SYMPTOMS
History of HIV infection or immunosuppression may be present.
Pulmonary findings are common and include tachypnea, decreased breath sounds, crackles, and dullness to percussion; extrapulmonary findings are dependent upon the site involved. Lymphadenopathy is common in all age groups.
Deformity of the spine with or without long-tract central nervous system signs suggests tuberculosis, as does joint destruction.
INVESTIGATIONS
Positive stains for acid-fast bacilli and/or culture of tuberculosis organisms.
Biopsy of the affected organ reveals caseating granulomas.
X-rays show destructive changes with deformity of the spine.
Malaria infection
SIGNS / SYMPTOMS
Tertian or quartan fever pattern typical. Renal failure and hemorrhagic complications can occur.
INVESTIGATIONS
Peripheral blood smear reveals Plasmodium parasite; malaria antigen detection tests positive.
Typhoid infection
SIGNS / SYMPTOMS
Patients usually appear toxic, with sustained high fever.
An erythematous maculopapular rash that blanches on pressure may be present.
INVESTIGATIONS
Blood or bone marrow culture results in isolation of Salmonella typhi or S paratyphi.
Septic arthritis
SIGNS / SYMPTOMS
Risk factors for infection, such as intravenous drug use and immunocompromise, may be present.
Hot, swollen, tender joint(s) present on physical exam.
INVESTIGATIONS
Synovial fluid microscopy shows neutrophils and may show gram-positive organisms (or acid-fast bacilli) but not brucellae.
Culture of blood and/or synovial fluid positive for causative organisms.
Rheumatoid arthritis
SIGNS / SYMPTOMS
Symmetric polyarthritis commonly affecting the small joints of the hands and feet.
Does not affect the lumbar spine or sacroiliac joints.
INVESTIGATIONS
Rheumatoid factor and anti-cyclic citrullinated peptide antibodies may be positive.
Hand radiographs reveal typical erosive changes.
Systemic lupus erythematosus
SIGNS / SYMPTOMS
Symmetric polyarthritis often affecting distal joints, accompanied by skin rashes, hair loss, hepatosplenomegaly, retinitis, neuropsychiatric problems, and serositis (e.g., pleural effusion).
INVESTIGATIONS
Positive antinuclear antibody; positive anti-double stranded DNA and anti-Smith antibodies confirm diagnosis.
Behcet syndrome
SIGNS / SYMPTOMS
Common in Middle Eastern and Mediterranean populations.
Presence of oral ulcers necessary for diagnosis.
Genital ulcers, skin lesions, and eye lesions are common.
INVESTIGATIONS
Pathergy testing results in formation of a pustule within 48 hours; negative serologic tests and cultures for brucellosis.
Gout
SIGNS / SYMPTOMS
Fever absent.
Involved joints are warm, red, and swollen. Usually, there is considerable joint tenderness and limited range of movement due to pain.
Hard subcutaneous nodules (tophi) over the extensor surface of the joint, especially over the elbows, knees, and Achilles tendons, may be present. Tophi may also be evident over the dorsal aspects of the hands and feet, and in the helix of the ears.
INVESTIGATIONS
Synovial fluid polarizing microscopy will reveal strongly negative, birefringent, needle-shaped crystals.
Pseudogout
SIGNS / SYMPTOMS
Fever absent.
Involved joints are warm, red, and swollen. Usually, there is considerable joint tenderness and limited range of movement due to pain.
INVESTIGATIONS
Calcium pyrophosphate dihydrate (CPPD) crystals in synovial fluid can be small, sparse, and difficult to find.
Osteoarthritis
SIGNS / SYMPTOMS
Fever absent.
Patients present with joint pain and stiffness that is typically worse with activity.
INVESTIGATIONS
Plain film x-ray of the affected joint usually demonstrates new bone formation (osteophytes), joint space narrowing, and subchondral sclerosis and cysts.
Granulomatous hepatitis
SIGNS / SYMPTOMS
Granulomas in the liver are associated with a number of disorders. Infectious disorders are the most important: bacterial (e.g., tuberculosis and other mycobacterial infections, tularemia, actinomycosis); fungal (e.g., histoplasmosis, cryptococcosis, blastomycosis); parasitic (e.g., schistosomiasis, toxoplasmosis, visceral larva migrans); less common viral infections (e.g., infectious mononucleosis, cytomegalovirus); and numerous others (e.g., Q fever, syphilis, cat-scratch disease).
Sarcoidosis is the most important noninfectious cause. Hepatic granulomas can also occur in polymyalgia rheumatica and other collagen-vascular diseases, and in Hodgkin disease and some other systemic conditions.
INVESTIGATIONS
Histology reveals conspicuous and frequent granulomas (caseating or noncaseating).
Lymphoma
SIGNS / SYMPTOMS
Usually presents with a painless mass in the neck, axilla, or inguinal region.
Typical exam findings include lymph node enlargement, with or without tenderness, and hepatosplenomegaly.
INVESTIGATIONS
Core biopsy of the lymph node or suspected tissue shows abnormal proliferation of lymphocytes.
HIV infection
SIGNS / SYMPTOMS
History of high-risk behavior (intravenous drug use, multiple sexual partners, unprotected sexual intercourse).
Herpes zoster, oral candidiasis, pronounced weight loss, and/or opportunistic infection (e.g., Pneumocystis jirovecii, tuberculosis) may be present.
INVESTIGATIONS
HIV antibodies positive; may be negative in early disease.
Mumps
SIGNS / SYMPTOMS
More common in children and young adults.
Orchitis is usually bilateral and typically accompanied by parotid gland swelling.
INVESTIGATIONS
Positive serum amylase tests (salivary or pancreatic origin); positive serum mumps IgM.
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