- Published on
Infectious Diseases and Microbiology: Postoperative Fever
Basics
Description
Postoperative fever is defined as a body temperature above 38°C (100.4°F) occurring after an invasive procedure. It is classified by timing: immediate (during surgery or within hours), acute (within the first postoperative week), subacute (1–4 weeks after surgery), and delayed (more than one month postoperatively). Most cases result from the inflammatory response to surgery and resolve spontaneously, but fever may signal a serious complication. Evaluation requires careful history, physical examination, and appropriate laboratory and imaging studies, including cultures and Gram stains when indicated. Early postoperative fever is frequently noninfectious; however, fever persisting beyond 96 hours is more likely infectious. Consider that patients may have been incubating community-acquired infection preoperatively. New or persistent fever beyond four days strongly suggests ongoing pathology or a new complication. Surgical wounds, catheter insertion sites, and all dressings must be inspected, and recent interventions such as blood transfusions reviewed.
Epidemiology
Drug fever is the most common noninfectious cause of postoperative fever, most often linked to antimicrobials and heparin. Pneumonia is a common cause after cardiac surgery and occurs in more than 5% of such patients. Sternal wound infections after cardiothoracic surgery occur in up to 5%, typically around postoperative day seven. Postoperative aspergillosis after cardiothoracic procedures carries very high mortality. Fever alone is a poor predictor of infection, with low sensitivity. Postsurgical mediastinitis has high mortality. In obstetrics and gynecology, bacterial vaginosis may increase postoperative infection risk.
General Prevention
Aggressive pulmonary hygiene, including incentive spirometry and mobilization, reduces pulmonary complications such as atelectasis.
Etiology
Common infectious causes include urinary tract infection, pneumonia, sinusitis, suppurative thrombophlebitis, catheter-related infections, and Clostridioides difficile–associated diarrhea. Noninfectious causes include deep venous thrombosis, pulmonary embolism, subarachnoid hemorrhage, gout, and fat embolism. Surgical site infections are uncommon within the first 1–3 days except for aggressive pathogens such as group A streptococci or clostridia, which can present early. Atelectasis is frequently blamed but likely coincidental rather than causal. Other serious causes include transplant rejection. Drug-induced fever is most often associated with beta-lactams, antiepileptics, and heparin. Inflammatory states such as acute myocardial infarction, pancreatitis, or acute respiratory distress syndrome may produce fever without infection. Endocrine emergencies such as adrenal insufficiency or thyrotoxicosis may also present with fever.
Diagnosis
Physical Examination
Drug fever lacks specific features and usually develops days after medication exposure; rash and eosinophilia are uncommon. Malignant hyperthermia typically occurs intraoperatively but may be delayed up to 24 hours and is associated with agents such as succinylcholine or volatile anesthetics. Neuroleptic malignant syndrome is associated with antipsychotics, particularly haloperidol. Withdrawal syndromes from alcohol, opioids, barbiturates, or benzodiazepines may cause fever hours to days after admission, and prior substance use history may not be readily available.
Diagnostic Tests and Interpretation
Laboratory Studies
Urinalysis and urine culture are recommended in patients with indwelling catheters longer than 72 hours. Procalcitonin has uncertain value in distinguishing bacterial causes of postoperative fever.
Imaging
Duplex ultrasonography with Doppler should be considered for new extremity swelling suggestive of deep venous thrombosis. Routine chest radiography is not required within the first 72 postoperative hours if fever is the only indication.
Diagnostic Procedures/Other
Wound swab cultures are rarely useful unless there is clear clinical evidence of infection. Suspected deep intraabdominal abscess may require imaging and, if inconclusive, surgical exploration.
Treatment
Medications
Antibiotics are generally not indicated for early postoperative fever without evidence of infection. Critically ill patients or those with hemodynamic instability should receive empiric broad-spectrum antibiotics after thorough evaluation, but therapy should be discontinued after 48 hours if no infectious source is identified. Atelectasis management includes coughing exercises, incentive spirometry, chest physiotherapy, beta-2 agonists, intermittent positive-pressure breathing, and nebulization. Empiric antifungal therapy is not recommended initially.
Ongoing Care and Follow-Up
Drug fever is diagnosed by exclusion when other causes are ruled out. Surgical wounds and invasive device sites must be repeatedly examined for signs of infection.
Complications
Postoperative infections increase morbidity and mortality, may lead to sepsis, impair wound healing, and cause respiratory failure and other serious outcomes.
Basics
Description
Postoperative fever is defined as a body temperature above 38°C (100.4°F) occurring after an invasive procedure. It is classified by timing: immediate (during surgery or within hours), acute (within the first postoperative week), subacute (1–4 weeks after surgery), and delayed (more than one month postoperatively). Most cases result from the inflammatory response to surgery and resolve spontaneously, but fever may signal a serious complication. Evaluation requires careful history, physical examination, and appropriate laboratory and imaging studies, including cultures and Gram stains when indicated. Early postoperative fever is frequently noninfectious; however, fever persisting beyond 96 hours is more likely infectious. Consider that patients may have been incubating community-acquired infection preoperatively. New or persistent fever beyond four days strongly suggests ongoing pathology or a new complication. Surgical wounds, catheter insertion sites, and all dressings must be inspected, and recent interventions such as blood transfusions reviewed.
Epidemiology
Drug fever is the most common noninfectious cause of postoperative fever, most often linked to antimicrobials and heparin. Pneumonia is a common cause after cardiac surgery and occurs in more than 5% of such patients. Sternal wound infections after cardiothoracic surgery occur in up to 5%, typically around postoperative day seven. Postoperative aspergillosis after cardiothoracic procedures carries very high mortality. Fever alone is a poor predictor of infection, with low sensitivity. Postsurgical mediastinitis has high mortality. In obstetrics and gynecology, bacterial vaginosis may increase postoperative infection risk.
General Prevention
Aggressive pulmonary hygiene, including incentive spirometry and mobilization, reduces pulmonary complications such as atelectasis.
Etiology
Common infectious causes include urinary tract infection, pneumonia, sinusitis, suppurative thrombophlebitis, catheter-related infections, and Clostridioides difficile–associated diarrhea. Noninfectious causes include deep venous thrombosis, pulmonary embolism, subarachnoid hemorrhage, gout, and fat embolism. Surgical site infections are uncommon within the first 1–3 days except for aggressive pathogens such as group A streptococci or clostridia, which can present early. Atelectasis is frequently blamed but likely coincidental rather than causal. Other serious causes include transplant rejection. Drug-induced fever is most often associated with beta-lactams, antiepileptics, and heparin. Inflammatory states such as acute myocardial infarction, pancreatitis, or acute respiratory distress syndrome may produce fever without infection. Endocrine emergencies such as adrenal insufficiency or thyrotoxicosis may also present with fever.
Diagnosis
Physical Examination
Drug fever lacks specific features and usually develops days after medication exposure; rash and eosinophilia are uncommon. Malignant hyperthermia typically occurs intraoperatively but may be delayed up to 24 hours and is associated with agents such as succinylcholine or volatile anesthetics. Neuroleptic malignant syndrome is associated with antipsychotics, particularly haloperidol. Withdrawal syndromes from alcohol, opioids, barbiturates, or benzodiazepines may cause fever hours to days after admission, and prior substance use history may not be readily available.
Diagnostic Tests and Interpretation
Laboratory Studies
Urinalysis and urine culture are recommended in patients with indwelling catheters longer than 72 hours. Procalcitonin has uncertain value in distinguishing bacterial causes of postoperative fever.
Imaging
Duplex ultrasonography with Doppler should be considered for new extremity swelling suggestive of deep venous thrombosis. Routine chest radiography is not required within the first 72 postoperative hours if fever is the only indication.
Diagnostic Procedures/Other
Wound swab cultures are rarely useful unless there is clear clinical evidence of infection. Suspected deep intraabdominal abscess may require imaging and, if inconclusive, surgical exploration.
Treatment
Medications
Antibiotics are generally not indicated for early postoperative fever without evidence of infection. Critically ill patients or those with hemodynamic instability should receive empiric broad-spectrum antibiotics after thorough evaluation, but therapy should be discontinued after 48 hours if no infectious source is identified. Atelectasis management includes coughing exercises, incentive spirometry, chest physiotherapy, beta-2 agonists, intermittent positive-pressure breathing, and nebulization. Empiric antifungal therapy is not recommended initially.
Ongoing Care and Follow-Up
Drug fever is diagnosed by exclusion when other causes are ruled out. Surgical wounds and invasive device sites must be repeatedly examined for signs of infection.
Complications
Postoperative infections increase morbidity and mortality, may lead to sepsis, impair wound healing, and cause respiratory failure and other serious outcomes.
- Published on
Infectious Diseases and Microbiology: Genital Lesions and Ulcers
Basics
Description
Genital lesions involve the reproductive organs and can result from a range of infectious and noninfectious conditions.
Epidemiology
Genital ulcers are the most frequent sexually transmitted cause of genital lesions. In North America and Europe, the leading sexually transmitted causes of genital ulcer disease are herpes simplex and syphilis. In the United States, a substantial proportion of people aged 14–49 have HSV-2 infection, and HSV-1 accounts for a significant minority of genital herpes cases. Chancroid is more common in Africa, Asia, and Latin America but can occur in sporadic U.S. outbreaks. Lymphogranuloma venereum is uncommon in industrialized countries, though outbreaks have been reported among men who have sex with men.
Risk Factors
About half of exposed sexual partners may acquire genital warts (HPV) after contact with an infected partner. Sexual transmission of syphilis can be high, with rates reported up to roughly one-third per exposure.
General Prevention
Risk reduction includes abstinence, consistent condom use, limiting partners, safer-sex practices, and HPV vaccination. Two HPV vaccines are available for females aged 9–26 that protect against HPV 6 and 11 (responsible for most genital warts) and HPV 16 and 18 (responsible for a large proportion of cervical cancers): the quadrivalent vaccine (Gardasil) and the bivalent vaccine (Cervarix). Quadrivalent vaccination in males aged 9–26 can reduce genital warts.
Etiology
Infectious Ulcers
Common causes include genital herpes, syphilis due to Treponema pallidum, chancroid due to Haemophilus ducreyi, lymphogranuloma venereum from Chlamydia trachomatis serovars L1–L3, donovanosis (granuloma inguinale) from Klebsiella granulomatis, and less commonly tuberculosis or tularemia. Additional reported etiologies include candidiasis, histoplasmosis, amebiasis, gonorrhea, and trichomoniasis. Acute or primary HIV infection can present with genital ulcers, and a notable minority of ulcer cases involve more than one pathogen.
Noninfectious Ulcers
Noninfectious causes include trauma, fixed drug eruption, malignancy, systemic lupus erythematosus, and Behçet disease.
Other Lesion Patterns
Papules may be due to candidiasis, molluscum contagiosum, scabies, syphilis, or condylomata acuminata from HPV, with types 6 and 11 most common and types 16, 18, 31, 33, and 35 linked to cervical dysplasia. Vesicles or bullae suggest herpes, impetigo, or scabies. Diffuse erythema may occur with candidiasis, erysipelas often after trauma or surgery, contact dermatitis, drug eruption, psoriasis, or trauma. Other patterns include benign cysts, nodules from hidradenitis or furunculosis, and crusted lesions from herpes or scabies
.
Commonly Associated Conditions
HIV and other sexually transmitted infections commonly coexist with genital lesions.
Diagnosis
History
Key points include time of onset, associated symptoms, immunodeficiency, prior sexually transmitted infections, prior similar lesions, and travel. Typical incubation periods vary by cause, including herpes within days but sometimes up to weeks, genital warts usually weeks to months, syphilis typically weeks but up to months, chancroid usually within a week but variable, donovanosis over weeks, molluscum potentially months, and ectoparasites such as pubic lice or scabies often after several weeks. Lesions appearing within hours of exposure suggest trauma, chemical irritation, or hypersensitivity. Itching is common early in herpes and with scabies or pubic lice, and mild pruritus can occur in secondary syphilis.
Physical Examination
Define lesion morphology and distribution, determine whether disease is localized or generalized, assess tenderness, lymphadenopathy, and any urethral or vaginal discharge, and examine buccal mucosa and perianal skin; pelvic examination or prostate assessment is often needed. Early herpes often begins as clustered vesicles on an erythematous base, may show umbilication, is typically very painful, and is often ulcerated by presentation. Pain is typical of herpes, chancroid, and tularemia, whereas donovanosis ulcers are usually painless. Ulcer base and borders can help narrow the differential: Behçet ulcers may be yellow and necrotic, chancroid bases are often necrotic, donovanosis can appear beefy red with hypertrophy, and syphilitic and herpetic ulcers may have cleaner bases; chancroid ulcers are classically nonindurated with irregular erythematous edges, syphilitic ulcers are indurated, and herpetic ulcers often have erythematous borders. Primary syphilis more often produces a solitary lesion, while chancroid often causes multiple ulcers of varying size. Behçet disease can cause recurrent, multiple genital ulcers involving scrotum or vulva and may be accompanied by recurrent oral ulcers and skin or eye disease, which may not occur simultaneously. Linear burrows suggest scabies, and reddish specks may reflect crab louse excreta. Urethral discharge suggests gonorrhea or reactive arthritis. In adults with genital lesions, inguinal lymphadenopathy supports consideration of chancroid, LGV, syphilis, herpes, lymphoma, or tuberculosis. LGV ulcers may be unnoticed and heal spontaneously, followed weeks later by painful inguinal lymphadenopathy and systemic symptoms, and untreated disease can progress to elephantiasis-like genital distortion. Lymphadenopathy tends to be unilateral in chancroid and LGV and more often bilateral in genital herpes. Painful perianal ulcers or mucosal ulcers seen on anoscopy should be treated presumptively for HSV and LGV. Molluscum contagiosum causes mildly contagious umbilicated papules up to about 1 cm, and advanced HIV may cause widespread or large lesions. Tuberculous genital lesions may appear as chronic minimally painful red, firm, nodular sores. Clinical appearance alone is often insufficient for diagnosis.
Diagnostic Tests and Interpretation
Laboratory Studies
All patients with genital, anal, or perianal ulcers should receive syphilis serology with dark-field examination when available, HSV testing by culture or PCR or type-specific serology, and HIV testing. If suspicion and culture capacity exist, obtain H. ducreyi culture for chancroid. Donovanosis can be supported by identifying intracellular Donovan bodies on Giemsa or Wright stain from lesion scrapings or biopsy, with biopsy favored when malignancy is possible. Chancroid culture can be sensitive but is limited by availability of selective media; a probable diagnosis relies on painful ulcers typical of chancroid with negative testing for syphilis and HSV. LGV diagnosis is supported by serology or by isolating C. trachomatis with confirmation of L1–L3 serovars. Molluscum can be confirmed by histology and electron microscopy. Chancres may be missed by patients, and early syphilis serology can be falsely negative; when diagnosis is uncertain or cancer is possible, biopsy is indicated.
Treatment
Medications
Chancroid can be treated with single-dose azithromycin 1 g orally or ceftriaxone 250 mg intramuscularly. Condylomata acuminata have no single best therapy; options include imiquimod 5% cream three times weekly for up to 16 weeks or podofilox 0.5% solution or gel twice daily for three days followed by one day off, repeated in cycles. Donovanosis can be treated for more than three weeks with trimethoprim-sulfamethoxazole, tetracycline, or doxycycline. Genital herpes is treated with acyclovir, famciclovir, or valacyclovir for 7–10 days, with intravenous acyclovir for severe disease. Tuberculous genital lesions require systemic antituberculosis therapy. LGV is treated with doxycycline 100 mg twice daily for 21 days. Molluscum contagiosum can be managed with lesion destruction via desiccation, cryotherapy, or curettage.
Complementary and Alternative Therapies
Alternative chancroid regimens include erythromycin for seven days or ciprofloxacin for three days. Wart management can include cryosurgery, excision, electrosurgery, or laser therapy. Donovanosis alternatives include prolonged ciprofloxacin, erythromycin, or chloramphenicol. LGV can also be treated with erythromycin four times daily for 21 days.
Ongoing Care and Follow-Up
Patients should be encouraged to have sexual partners evaluated and treated. HIV testing should be performed at diagnosis and repeated with syphilis serology about three months later if initially negative. Consider cervical cytology screening for patients evaluated for sexually transmitted infections who have not had a Pap smear within the past year, and counsel patients with HPV on the need for ongoing screening.
Pediatric Considerations
Sexually transmitted genital lesions in a child require evaluation for sexual abuse.
Complications
Untreated primary syphilis can disseminate and progress to secondary disease within weeks. Chancroid, genital herpes, and syphilis increase susceptibility to HIV transmission.
Basics
Description
Genital lesions involve the reproductive organs and can result from a range of infectious and noninfectious conditions.
Epidemiology
Genital ulcers are the most frequent sexually transmitted cause of genital lesions. In North America and Europe, the leading sexually transmitted causes of genital ulcer disease are herpes simplex and syphilis. In the United States, a substantial proportion of people aged 14–49 have HSV-2 infection, and HSV-1 accounts for a significant minority of genital herpes cases. Chancroid is more common in Africa, Asia, and Latin America but can occur in sporadic U.S. outbreaks. Lymphogranuloma venereum is uncommon in industrialized countries, though outbreaks have been reported among men who have sex with men.
Risk Factors
About half of exposed sexual partners may acquire genital warts (HPV) after contact with an infected partner. Sexual transmission of syphilis can be high, with rates reported up to roughly one-third per exposure.
General Prevention
Risk reduction includes abstinence, consistent condom use, limiting partners, safer-sex practices, and HPV vaccination. Two HPV vaccines are available for females aged 9–26 that protect against HPV 6 and 11 (responsible for most genital warts) and HPV 16 and 18 (responsible for a large proportion of cervical cancers): the quadrivalent vaccine (Gardasil) and the bivalent vaccine (Cervarix). Quadrivalent vaccination in males aged 9–26 can reduce genital warts.
Etiology
Infectious Ulcers
Common causes include genital herpes, syphilis due to Treponema pallidum, chancroid due to Haemophilus ducreyi, lymphogranuloma venereum from Chlamydia trachomatis serovars L1–L3, donovanosis (granuloma inguinale) from Klebsiella granulomatis, and less commonly tuberculosis or tularemia. Additional reported etiologies include candidiasis, histoplasmosis, amebiasis, gonorrhea, and trichomoniasis. Acute or primary HIV infection can present with genital ulcers, and a notable minority of ulcer cases involve more than one pathogen.
Noninfectious Ulcers
Noninfectious causes include trauma, fixed drug eruption, malignancy, systemic lupus erythematosus, and Behçet disease.
Other Lesion Patterns
Papules may be due to candidiasis, molluscum contagiosum, scabies, syphilis, or condylomata acuminata from HPV, with types 6 and 11 most common and types 16, 18, 31, 33, and 35 linked to cervical dysplasia. Vesicles or bullae suggest herpes, impetigo, or scabies. Diffuse erythema may occur with candidiasis, erysipelas often after trauma or surgery, contact dermatitis, drug eruption, psoriasis, or trauma. Other patterns include benign cysts, nodules from hidradenitis or furunculosis, and crusted lesions from herpes or scabies
.
Commonly Associated Conditions
HIV and other sexually transmitted infections commonly coexist with genital lesions.
Diagnosis
History
Key points include time of onset, associated symptoms, immunodeficiency, prior sexually transmitted infections, prior similar lesions, and travel. Typical incubation periods vary by cause, including herpes within days but sometimes up to weeks, genital warts usually weeks to months, syphilis typically weeks but up to months, chancroid usually within a week but variable, donovanosis over weeks, molluscum potentially months, and ectoparasites such as pubic lice or scabies often after several weeks. Lesions appearing within hours of exposure suggest trauma, chemical irritation, or hypersensitivity. Itching is common early in herpes and with scabies or pubic lice, and mild pruritus can occur in secondary syphilis.
Physical Examination
Define lesion morphology and distribution, determine whether disease is localized or generalized, assess tenderness, lymphadenopathy, and any urethral or vaginal discharge, and examine buccal mucosa and perianal skin; pelvic examination or prostate assessment is often needed. Early herpes often begins as clustered vesicles on an erythematous base, may show umbilication, is typically very painful, and is often ulcerated by presentation. Pain is typical of herpes, chancroid, and tularemia, whereas donovanosis ulcers are usually painless. Ulcer base and borders can help narrow the differential: Behçet ulcers may be yellow and necrotic, chancroid bases are often necrotic, donovanosis can appear beefy red with hypertrophy, and syphilitic and herpetic ulcers may have cleaner bases; chancroid ulcers are classically nonindurated with irregular erythematous edges, syphilitic ulcers are indurated, and herpetic ulcers often have erythematous borders. Primary syphilis more often produces a solitary lesion, while chancroid often causes multiple ulcers of varying size. Behçet disease can cause recurrent, multiple genital ulcers involving scrotum or vulva and may be accompanied by recurrent oral ulcers and skin or eye disease, which may not occur simultaneously. Linear burrows suggest scabies, and reddish specks may reflect crab louse excreta. Urethral discharge suggests gonorrhea or reactive arthritis. In adults with genital lesions, inguinal lymphadenopathy supports consideration of chancroid, LGV, syphilis, herpes, lymphoma, or tuberculosis. LGV ulcers may be unnoticed and heal spontaneously, followed weeks later by painful inguinal lymphadenopathy and systemic symptoms, and untreated disease can progress to elephantiasis-like genital distortion. Lymphadenopathy tends to be unilateral in chancroid and LGV and more often bilateral in genital herpes. Painful perianal ulcers or mucosal ulcers seen on anoscopy should be treated presumptively for HSV and LGV. Molluscum contagiosum causes mildly contagious umbilicated papules up to about 1 cm, and advanced HIV may cause widespread or large lesions. Tuberculous genital lesions may appear as chronic minimally painful red, firm, nodular sores. Clinical appearance alone is often insufficient for diagnosis.
Diagnostic Tests and Interpretation
Laboratory Studies
All patients with genital, anal, or perianal ulcers should receive syphilis serology with dark-field examination when available, HSV testing by culture or PCR or type-specific serology, and HIV testing. If suspicion and culture capacity exist, obtain H. ducreyi culture for chancroid. Donovanosis can be supported by identifying intracellular Donovan bodies on Giemsa or Wright stain from lesion scrapings or biopsy, with biopsy favored when malignancy is possible. Chancroid culture can be sensitive but is limited by availability of selective media; a probable diagnosis relies on painful ulcers typical of chancroid with negative testing for syphilis and HSV. LGV diagnosis is supported by serology or by isolating C. trachomatis with confirmation of L1–L3 serovars. Molluscum can be confirmed by histology and electron microscopy. Chancres may be missed by patients, and early syphilis serology can be falsely negative; when diagnosis is uncertain or cancer is possible, biopsy is indicated.
Treatment
Medications
Chancroid can be treated with single-dose azithromycin 1 g orally or ceftriaxone 250 mg intramuscularly. Condylomata acuminata have no single best therapy; options include imiquimod 5% cream three times weekly for up to 16 weeks or podofilox 0.5% solution or gel twice daily for three days followed by one day off, repeated in cycles. Donovanosis can be treated for more than three weeks with trimethoprim-sulfamethoxazole, tetracycline, or doxycycline. Genital herpes is treated with acyclovir, famciclovir, or valacyclovir for 7–10 days, with intravenous acyclovir for severe disease. Tuberculous genital lesions require systemic antituberculosis therapy. LGV is treated with doxycycline 100 mg twice daily for 21 days. Molluscum contagiosum can be managed with lesion destruction via desiccation, cryotherapy, or curettage.
Complementary and Alternative Therapies
Alternative chancroid regimens include erythromycin for seven days or ciprofloxacin for three days. Wart management can include cryosurgery, excision, electrosurgery, or laser therapy. Donovanosis alternatives include prolonged ciprofloxacin, erythromycin, or chloramphenicol. LGV can also be treated with erythromycin four times daily for 21 days.
Ongoing Care and Follow-Up
Patients should be encouraged to have sexual partners evaluated and treated. HIV testing should be performed at diagnosis and repeated with syphilis serology about three months later if initially negative. Consider cervical cytology screening for patients evaluated for sexually transmitted infections who have not had a Pap smear within the past year, and counsel patients with HPV on the need for ongoing screening.
Pediatric Considerations
Sexually transmitted genital lesions in a child require evaluation for sexual abuse.
Complications
Untreated primary syphilis can disseminate and progress to secondary disease within weeks. Chancroid, genital herpes, and syphilis increase susceptibility to HIV transmission.
- Published on
Infectious Diseases and Microbiology: Fever of Unknown Origin
Basics
Description
Fever of unknown origin (FUO) describes persistent fever that lasts longer than expected for a typical acute febrile illness and is meant to exclude self-limited infections, conditions identified on basic initial testing, and benign fevers below 38.3°C. Current criteria, revised from the 1961 Petersdorf and Beeson definition, require illness duration of at least three weeks, documented temperatures above 38.3°C on multiple occasions, and no diagnosis despite a thorough evaluation. Durack and Street proposed FUO subtypes reflecting differing causes and workups: classical FUO, immune-deficient FUO, healthcare-associated FUO, and HIV-related FUO. Using this framework, immune-deficient patients, hospitalized patients who were afebrile before admission, and patients with HIV may meet FUO criteria after three to five inpatient days of evaluation with 48 hours of negative cultures.
Approach to the Patient
FUO is clinically difficult for both patients and clinicians, and management centers on identifying a cause, reaching a diagnosis efficiently and safely with appropriate testing, and initiating targeted therapy once a diagnosis is established or, when necessary, performing a therapeutic trial. Evaluation should be individualized to avoid both excessive testing for unlikely causes and missed evaluation of likely ones, so rigid algorithms are discouraged. Key aims are to confirm true fever and define its pattern, assess illness tempo and severity, look for localizing symptoms, place the illness in context of comorbidities and medications, and identify exposure risks such as travel, occupational and sexual history, animal contact, vaccination status, and intravenous drug use. Minimum baseline evaluation should include detailed history, repeated physical examination, complete blood count with smear, differential and platelets, routine chemistries including liver enzymes, LDH and bilirubin, urinalysis with microscopy and culture, chest radiograph, ESR and CRP, ANA, rheumatoid factor and anti-CCP, three sets of blood cultures obtained off antibiotics, tuberculosis testing with TST or IGRA, CT abdomen and pelvis, and infectious serologies guided by the clinical scenario.
Special Populations
Geriatric Considerations
Consider polymyalgia rheumatica and recognize that the distribution of undiagnosed etiologies differs in older adults.
Pediatric Considerations
Herpesviruses HHV-6/7/8 are common in infants and children. Ultrasound is preferred over CT to limit radiation and because pediatric imaging resolution is favorable. Connective tissue disease and neoplasia are uncommon under 12 months, Kawasaki disease is common under 5 years, Still’s disease often affects children and young adults, and arthritis in children should be treated as a marker of potentially serious disease. Periodic fever and other entities to consider include hyper-IgD syndrome, cyclic neutropenia, and nephroma.
Pregnancy Considerations
Pregnancy increases venous thromboembolism risk. Consider septic pelvic thrombophlebitis after obstetric surgery, sexually transmitted infections including HIV and syphilis, and pyometra.
Epidemiology
True FUO is uncommon. Reported etiologic frequencies vary by population, geography, institution, age, local disease prevalence, and practice patterns. Over time, the proportion of infectious and malignant causes has decreased while the proportion of undiagnosed cases has increased.
Diagnosis
FUO evaluation relies on iterative history-taking, repeated examinations, laboratory studies, and imaging.
History
History should cover alcohol use, medications, occupational and sexual exposures, pets, travel, family conditions, and prior illnesses. Although fever patterns are described for many disorders, truly distinctive patterns are rare in practice; classic patterns such as malaria are uncommon in many settings, and patterns considered characteristic for other diseases, such as Pel–Ebstein fever in lymphoma, are infrequently observed.
Physical Examination
Repeated comprehensive examination is central and should specifically assess the oropharynx for dental abscess, thyroid for thyroiditis, temporal regions for arteritis, cardiac auscultation for murmurs suggesting endocarditis or atrial myxoma, skin for vasculitis and Whipple disease clues, all wounds and vascular access sites with dressings removed for inspection, regional lymph nodes, and the genitoperineal region, sometimes requiring rectal or vaginal examination. Relative bradycardia can be a clue but is nonspecific and occurs in diverse conditions including brucellosis, drug fever, factitious fever, hepatitis A, Legionella infection, leptospirosis, malignancy, psittacosis, subacute necrotizing lymphadenitis, and typhoid fever. Fever from solid tumors and many connective tissue diseases may abate with NSAIDs, whereas fever from other causes may not. Symptoms such as sweats, chills, and weight loss do not reliably distinguish etiologies. Clues suggesting factitious fever include lack of tachycardia or tachypnea, temperatures exceeding 41°C, absent diurnal variation, and lack of sweating after defervescence.
Diagnostic Tests and Interpretation
Laboratory Studies
Noninvasive tests yield a diagnosis in roughly one-quarter of cases and include serologies for infectious and rheumatologic disease, biochemical markers such as ferritin for Still’s disease, and genetic markers such as those used for familial Mediterranean fever.
Imaging
Imaging is primarily used to localize targets for further evaluation. Abdominal CT has improved diagnostic yield when followed by invasive sampling, though false negatives can occur even with solid-organ abscesses. MRI is preferred when spinal or paraspinal pathology is suspected. Nuclear imaging with gallium-67 or indium-111 labeled leukocytes can sometimes help when infection or malignancy is suspected, but limitations include false-negative gallium scans in secondarily infected lesions, poor detection of splenic abscess due to background uptake, and low positive predictive value with indium studies. FDG PET/CT can help establish malignant, inflammatory, or infectious diagnoses in at least one-third of cases. If imaging and serologies are unrevealing, invasive investigations such as liver and bone marrow biopsy should be considered, and fewer than half of diagnoses are ultimately made via biopsy or laparotomy. Temporal artery biopsy is often high yield in older adults with markedly elevated ESR even without obvious local symptoms. Disseminated tuberculosis is a highly treatable lethal cause of FUO and warrants aggressive pursuit; TST and IGRA can be negative in up to half of cases, sputum smears are only intermittently positive, and confirmation often requires biopsy of lymph node, bone marrow, or liver. Excisional lymph node biopsy is helpful when nodes are enlarged, though inguinal nodes are commonly palpable and usually not diagnostically useful.
Differential Diagnosis
The major etiologic categories and approximate frequencies include infections, malignancies, connective tissue or inflammatory disorders, miscellaneous causes, and undiagnosed cases. Unusual presentations of common diseases and conditions that are difficult to confirm account for more FUO cases than truly rare diseases, and thinking in terms of FUO subtype helps prioritize causes.
Classical FUO
Common infectious drivers remain tuberculosis, bacterial endocarditis, and intraabdominal collections. Systemic bacterial causes include bartonellosis, brucellosis, Campylobacter infection, cat-scratch disease or bacillary angiomatosis, ehrlichiosis, gonococcemia, HACEK organisms, Legionella infection, leptospirosis, listeriosis, Lyme disease, meningococcemia, rat-bite fever, relapsing fever due to Borrelia recurrentis, salmonellosis including typhoid, syphilis, tularemia, and yersiniosis, along with chlamydial, fungal, parasitic, and viral infections. Localized infections include intravascular infections such as endocarditis, aortitis, catheter infections, septic jugular phlebitis, and vascular graft infection; intraabdominal infections such as appendicitis, cholangitis, cholecystitis, diverticulitis, and diverse abscesses (subphrenic, hepatic, splenic, pancreatic, perinephric, pelvic), mesenteric lymphadenitis, pelvic inflammatory disease, and pyometra; prosthesis-related infections involving joint prostheses, pacemakers, defibrillators, shunts, and vascular access; and other focal infections including dental, intracranial, pulmonary, mastoid, middle ear, sinus, prostatic, and wound infections. Common noninfectious causes include malignancies such as renal cell carcinoma, hepatocellular carcinoma, Hodgkin and non-Hodgkin lymphoma, colon cancer, leukemia, malignant histiocytosis, pancreatic cancer, and sarcoma; benign tumors such as atrial myxoma; inflammatory disorders such as adult Still’s disease, Behçet syndrome, and cryoglobulinemia; and miscellaneous conditions including neuroleptic malignant syndrome, hematoma, recurrent pulmonary embolism, aortic dissection, post–myocardial infarction fever syndromes, subacute thyroiditis, hyperthyroidism, adrenal insufficiency, drug fever, factitious fever, gout, pseudogout, hypersensitivity pneumonitis, stroke, familial Mediterranean fever, and pheochromocytoma.
Healthcare-Associated FUO
Infectious causes include intravascular catheter infection, septic thrombophlebitis, prosthetic device infection, deep postoperative wound infections and intraabdominal collections, C. difficile colitis that may present with ileus rather than diarrhea in severe disease, septic pelvic thrombophlebitis after obstetric or gynecologic surgery, acalculous cholecystitis, and ICU-associated sinusitis related to nasogastric tubes and endotracheal intubation. Miscellaneous causes include venous thromboembolism, drug fever often without rash or eosinophilia and commonly triggered by antimicrobials and multiple other medication classes, factitious fever, and postoperative inflammatory fever without a defined diagnosis.
Immune-Deficient FUO
Most cases are infectious, with pathogen identification in a large fraction, and the likely infections depend on the type and duration of immunodeficiency. Persistent fever can reflect progressive or relapsed malignancy in hematology-oncology patients, inflammatory causes such as graft-versus-host disease, or miscellaneous etiologies including venous thromboembolism, drug fever, and adrenal insufficiency.
HIV-Related FUO
Most cases are infectious, though FUO has decreased in the antiretroviral era due to fewer opportunistic infections, and likely etiologies depend strongly on CD4 count. Scenarios include HIV seroconversion illness, opportunistic infections such as mycobacterial disease, Pneumocystis jirovecii, cytomegalovirus, toxoplasmosis, histoplasmosis, and leishmaniasis, inflammatory syndromes such as immune reconstitution, Castleman disease, and hemophagocytic lymphohistiocytosis, malignancies such as lymphoma and Kaposi sarcoma, and drug fever.
Treatment
Medications
Management is determined by the underlying cause. If TST or IGRA is positive or if granulomatous disease with possible anergy is suspected, a therapeutic trial for tuberculosis is recommended and may be continued for up to six weeks; persistent fever beyond this period suggests an alternate diagnosis. Glucocorticoids and NSAIDs can suppress fever and obscure diagnosis while allowing infection to progress and should be avoided unless infection has largely been excluded. In severely immune-deficient patients, empiric antimicrobial therapy is often necessary because infections are common and associated with high mortality.
Ongoing Care and Follow-Up
Hospitalized patients with FUO require close monitoring for evolving symptoms or new physical findings that may provide diagnostic direction.
Basics
Description
Fever of unknown origin (FUO) describes persistent fever that lasts longer than expected for a typical acute febrile illness and is meant to exclude self-limited infections, conditions identified on basic initial testing, and benign fevers below 38.3°C. Current criteria, revised from the 1961 Petersdorf and Beeson definition, require illness duration of at least three weeks, documented temperatures above 38.3°C on multiple occasions, and no diagnosis despite a thorough evaluation. Durack and Street proposed FUO subtypes reflecting differing causes and workups: classical FUO, immune-deficient FUO, healthcare-associated FUO, and HIV-related FUO. Using this framework, immune-deficient patients, hospitalized patients who were afebrile before admission, and patients with HIV may meet FUO criteria after three to five inpatient days of evaluation with 48 hours of negative cultures.
Approach to the Patient
FUO is clinically difficult for both patients and clinicians, and management centers on identifying a cause, reaching a diagnosis efficiently and safely with appropriate testing, and initiating targeted therapy once a diagnosis is established or, when necessary, performing a therapeutic trial. Evaluation should be individualized to avoid both excessive testing for unlikely causes and missed evaluation of likely ones, so rigid algorithms are discouraged. Key aims are to confirm true fever and define its pattern, assess illness tempo and severity, look for localizing symptoms, place the illness in context of comorbidities and medications, and identify exposure risks such as travel, occupational and sexual history, animal contact, vaccination status, and intravenous drug use. Minimum baseline evaluation should include detailed history, repeated physical examination, complete blood count with smear, differential and platelets, routine chemistries including liver enzymes, LDH and bilirubin, urinalysis with microscopy and culture, chest radiograph, ESR and CRP, ANA, rheumatoid factor and anti-CCP, three sets of blood cultures obtained off antibiotics, tuberculosis testing with TST or IGRA, CT abdomen and pelvis, and infectious serologies guided by the clinical scenario.
Special Populations
Geriatric Considerations
Consider polymyalgia rheumatica and recognize that the distribution of undiagnosed etiologies differs in older adults.
Pediatric Considerations
Herpesviruses HHV-6/7/8 are common in infants and children. Ultrasound is preferred over CT to limit radiation and because pediatric imaging resolution is favorable. Connective tissue disease and neoplasia are uncommon under 12 months, Kawasaki disease is common under 5 years, Still’s disease often affects children and young adults, and arthritis in children should be treated as a marker of potentially serious disease. Periodic fever and other entities to consider include hyper-IgD syndrome, cyclic neutropenia, and nephroma.
Pregnancy Considerations
Pregnancy increases venous thromboembolism risk. Consider septic pelvic thrombophlebitis after obstetric surgery, sexually transmitted infections including HIV and syphilis, and pyometra.
Epidemiology
True FUO is uncommon. Reported etiologic frequencies vary by population, geography, institution, age, local disease prevalence, and practice patterns. Over time, the proportion of infectious and malignant causes has decreased while the proportion of undiagnosed cases has increased.
Diagnosis
FUO evaluation relies on iterative history-taking, repeated examinations, laboratory studies, and imaging.
History
History should cover alcohol use, medications, occupational and sexual exposures, pets, travel, family conditions, and prior illnesses. Although fever patterns are described for many disorders, truly distinctive patterns are rare in practice; classic patterns such as malaria are uncommon in many settings, and patterns considered characteristic for other diseases, such as Pel–Ebstein fever in lymphoma, are infrequently observed.
Physical Examination
Repeated comprehensive examination is central and should specifically assess the oropharynx for dental abscess, thyroid for thyroiditis, temporal regions for arteritis, cardiac auscultation for murmurs suggesting endocarditis or atrial myxoma, skin for vasculitis and Whipple disease clues, all wounds and vascular access sites with dressings removed for inspection, regional lymph nodes, and the genitoperineal region, sometimes requiring rectal or vaginal examination. Relative bradycardia can be a clue but is nonspecific and occurs in diverse conditions including brucellosis, drug fever, factitious fever, hepatitis A, Legionella infection, leptospirosis, malignancy, psittacosis, subacute necrotizing lymphadenitis, and typhoid fever. Fever from solid tumors and many connective tissue diseases may abate with NSAIDs, whereas fever from other causes may not. Symptoms such as sweats, chills, and weight loss do not reliably distinguish etiologies. Clues suggesting factitious fever include lack of tachycardia or tachypnea, temperatures exceeding 41°C, absent diurnal variation, and lack of sweating after defervescence.
Diagnostic Tests and Interpretation
Laboratory Studies
Noninvasive tests yield a diagnosis in roughly one-quarter of cases and include serologies for infectious and rheumatologic disease, biochemical markers such as ferritin for Still’s disease, and genetic markers such as those used for familial Mediterranean fever.
Imaging
Imaging is primarily used to localize targets for further evaluation. Abdominal CT has improved diagnostic yield when followed by invasive sampling, though false negatives can occur even with solid-organ abscesses. MRI is preferred when spinal or paraspinal pathology is suspected. Nuclear imaging with gallium-67 or indium-111 labeled leukocytes can sometimes help when infection or malignancy is suspected, but limitations include false-negative gallium scans in secondarily infected lesions, poor detection of splenic abscess due to background uptake, and low positive predictive value with indium studies. FDG PET/CT can help establish malignant, inflammatory, or infectious diagnoses in at least one-third of cases. If imaging and serologies are unrevealing, invasive investigations such as liver and bone marrow biopsy should be considered, and fewer than half of diagnoses are ultimately made via biopsy or laparotomy. Temporal artery biopsy is often high yield in older adults with markedly elevated ESR even without obvious local symptoms. Disseminated tuberculosis is a highly treatable lethal cause of FUO and warrants aggressive pursuit; TST and IGRA can be negative in up to half of cases, sputum smears are only intermittently positive, and confirmation often requires biopsy of lymph node, bone marrow, or liver. Excisional lymph node biopsy is helpful when nodes are enlarged, though inguinal nodes are commonly palpable and usually not diagnostically useful.
Differential Diagnosis
The major etiologic categories and approximate frequencies include infections, malignancies, connective tissue or inflammatory disorders, miscellaneous causes, and undiagnosed cases. Unusual presentations of common diseases and conditions that are difficult to confirm account for more FUO cases than truly rare diseases, and thinking in terms of FUO subtype helps prioritize causes.
Classical FUO
Common infectious drivers remain tuberculosis, bacterial endocarditis, and intraabdominal collections. Systemic bacterial causes include bartonellosis, brucellosis, Campylobacter infection, cat-scratch disease or bacillary angiomatosis, ehrlichiosis, gonococcemia, HACEK organisms, Legionella infection, leptospirosis, listeriosis, Lyme disease, meningococcemia, rat-bite fever, relapsing fever due to Borrelia recurrentis, salmonellosis including typhoid, syphilis, tularemia, and yersiniosis, along with chlamydial, fungal, parasitic, and viral infections. Localized infections include intravascular infections such as endocarditis, aortitis, catheter infections, septic jugular phlebitis, and vascular graft infection; intraabdominal infections such as appendicitis, cholangitis, cholecystitis, diverticulitis, and diverse abscesses (subphrenic, hepatic, splenic, pancreatic, perinephric, pelvic), mesenteric lymphadenitis, pelvic inflammatory disease, and pyometra; prosthesis-related infections involving joint prostheses, pacemakers, defibrillators, shunts, and vascular access; and other focal infections including dental, intracranial, pulmonary, mastoid, middle ear, sinus, prostatic, and wound infections. Common noninfectious causes include malignancies such as renal cell carcinoma, hepatocellular carcinoma, Hodgkin and non-Hodgkin lymphoma, colon cancer, leukemia, malignant histiocytosis, pancreatic cancer, and sarcoma; benign tumors such as atrial myxoma; inflammatory disorders such as adult Still’s disease, Behçet syndrome, and cryoglobulinemia; and miscellaneous conditions including neuroleptic malignant syndrome, hematoma, recurrent pulmonary embolism, aortic dissection, post–myocardial infarction fever syndromes, subacute thyroiditis, hyperthyroidism, adrenal insufficiency, drug fever, factitious fever, gout, pseudogout, hypersensitivity pneumonitis, stroke, familial Mediterranean fever, and pheochromocytoma.
Healthcare-Associated FUO
Infectious causes include intravascular catheter infection, septic thrombophlebitis, prosthetic device infection, deep postoperative wound infections and intraabdominal collections, C. difficile colitis that may present with ileus rather than diarrhea in severe disease, septic pelvic thrombophlebitis after obstetric or gynecologic surgery, acalculous cholecystitis, and ICU-associated sinusitis related to nasogastric tubes and endotracheal intubation. Miscellaneous causes include venous thromboembolism, drug fever often without rash or eosinophilia and commonly triggered by antimicrobials and multiple other medication classes, factitious fever, and postoperative inflammatory fever without a defined diagnosis.
Immune-Deficient FUO
Most cases are infectious, with pathogen identification in a large fraction, and the likely infections depend on the type and duration of immunodeficiency. Persistent fever can reflect progressive or relapsed malignancy in hematology-oncology patients, inflammatory causes such as graft-versus-host disease, or miscellaneous etiologies including venous thromboembolism, drug fever, and adrenal insufficiency.
HIV-Related FUO
Most cases are infectious, though FUO has decreased in the antiretroviral era due to fewer opportunistic infections, and likely etiologies depend strongly on CD4 count. Scenarios include HIV seroconversion illness, opportunistic infections such as mycobacterial disease, Pneumocystis jirovecii, cytomegalovirus, toxoplasmosis, histoplasmosis, and leishmaniasis, inflammatory syndromes such as immune reconstitution, Castleman disease, and hemophagocytic lymphohistiocytosis, malignancies such as lymphoma and Kaposi sarcoma, and drug fever.
Treatment
Medications
Management is determined by the underlying cause. If TST or IGRA is positive or if granulomatous disease with possible anergy is suspected, a therapeutic trial for tuberculosis is recommended and may be continued for up to six weeks; persistent fever beyond this period suggests an alternate diagnosis. Glucocorticoids and NSAIDs can suppress fever and obscure diagnosis while allowing infection to progress and should be avoided unless infection has largely been excluded. In severely immune-deficient patients, empiric antimicrobial therapy is often necessary because infections are common and associated with high mortality.
Ongoing Care and Follow-Up
Hospitalized patients with FUO require close monitoring for evolving symptoms or new physical findings that may provide diagnostic direction.
- Published on
Infectious Diseases and Microbiology: Ear Pain
Basics
Description
Otalgia denotes pain originating in or perceived in the ear. Evaluation should consider patient age and associated symptoms such as sore throat, fever, headache, visual changes, and symptom duration. A systematic ear examination is essential, beginning with the auricle and external auditory meatus, followed by inspection of the auditory canal and tympanic membrane to guide the differential diagnosis. A complete head and neck examination may uncover lymphadenopathy, pharyngeal or nasal inflammation, thyroid disease, or dental and oral pathology. Cerumen can obstruct visualization of the tympanic membrane and should be gently removed when necessary. Any exudate within the auditory canal should be cultured. Pain elicited by movement of the pinna suggests otitis externa, foreign body, or impacted cerumen. Perichondritis, an infectious process of the outer ear cartilage, must be differentiated from relapsing polychondritis, a noninfectious rheumatologic condition.
Epidemiology
Approximately half of ear pain cases are referred from non-otologic sources. Acute otitis externa, commonly termed swimmer’s ear, occurs more frequently during summer months. Recurrent acute otitis media affects about one-fifth of children. Head and neck malignancies typically occur after age 50 but may present earlier, even without classic risk factors; several forms of nasopharyngeal carcinoma are associated with Epstein–Barr virus infection. Auricular cellulitis often follows minor trauma. Perichondritis usually develops after burns, trauma, or upper-ear piercings and is most commonly caused by Pseudomonas aeruginosa or Staphylococcus aureus. Chronic otitis externa often results from repeated minor trauma such as scratching or cotton swab use, and chronic middle-ear drainage may be mistaken for this condition. Malignant otitis externa is a destructive infection of the external canal and skull base.
Etiology
Ear pain is frequently referred because the ear receives sensory innervation from cranial nerves V, VII, VIII, IX, and X. Referred otalgia may arise from dental disease, gingival abscesses, nasopharyngeal or laryngeal inflammation or tumors, sinusitis, temporomandibular joint disorders, tonsillitis, tongue lesions, cervical spine disease, neural irritation such as trigeminal neuralgia or acoustic neuroma, gastroesophageal reflux in infants, thyroiditis, lateral sinus thrombosis, posterior fossa inflammation, or medication effects. Primary ear pathology causing otalgia includes acute or chronic otitis media, tympanic membrane rupture, anterior canal wall fracture, mastoiditis, Ménière disease, and eustachian tube dysfunction. Malignant otitis externa is almost always due to Pseudomonas aeruginosa. Otalgia may also accompany migraine, atypical facial pain, and herpes simplex infection of cranial nerves V, VII, or IX. Herpes zoster affecting the external auditory canal may produce ipsilateral facial paralysis, known as Ramsay Hunt syndrome, from involvement of the geniculate ganglion. Facial nerve palsy may also occur with Lyme disease. Neoplasms of the infratemporal fossa may present solely with ear pain. Acute otitis externa is most often caused by Pseudomonas aeruginosa, Staphylococcus aureus, or streptococcal species, with swimming and canal trauma as major risk factors.
Diagnosis
Clinical Manifestations
Auricular cellulitis presents with a swollen, erythematous, warm, mildly tender ear. Perichondritis causes marked swelling, redness, heat, and severe tenderness of the pinna with relative sparing of the lobule. Chronic otitis externa more commonly causes itching than pain. Nasopharyngeal carcinoma may be asymptomatic early but often produces unilateral serous otitis media from eustachian tube obstruction, nasal blockage, or epistaxis, and advanced disease may cause cranial nerve palsies, especially involving nerves III, IV, VI, and VII. Malignant otitis externa typically affects elderly patients with diabetes or individuals with HIV and presents with severe otalgia, otorrhea, possible hearing loss, tender pinna, trismus from temporomandibular involvement, and sometimes cranial nerve palsies, most often of nerve VII. Fever and weight loss are uncommon. Examination reveals canal edema, erythema, purulent discharge, debris, and granulation tissue. Vesicular lesions in the external canal suggest herpes zoster and warrant evaluation for facial nerve palsy. Hearing loss with abnormal tympanic membrane findings indicates serous or bacterial otitis media or cholesteatoma. Nasal polyps, marked septal deviation, or nasopharyngeal tumors may be associated with otitis media.
Physical Examination
Findings such as an erythematous canal with discharge, preauricular lymphadenopathy, and pain on tragal or pinna manipulation suggest otitis externa. Fever, irritability in children, and a bulging or erythematous tympanic membrane with loss of the cone of light indicate otitis media, sometimes with canal pus if perforation is present. Altered mental status or meningeal signs such as headache and neck stiffness indicate possible central nervous system involvement and require urgent management.
Diagnostic Tests and Interpretation
Laboratory Studies
Peripheral leukocytosis is uncommon in malignant otitis externa, whereas erythrocyte sedimentation rate is typically elevated. Cerebrospinal fluid analysis may occasionally show pleocytosis and increased protein.
Imaging
Dental pathology can be assessed with panoramic radiography. In malignant otitis externa, CT of the temporal bone or mastoid often demonstrates bony erosion and new bone formation, while MRI more accurately defines soft-tissue extension and skull-base involvement.
Treatment
Medications
Acute otitis externa is managed with careful canal cleaning and topical therapy using antiseptics or antibiotic drops such as polymyxin–neomycin, along with counseling on ear hygiene and water avoidance. Malignant otitis externa requires urgent otolaryngology consultation and prolonged antipseudomonal therapy with agents such as cefepime, ceftazidime, carbapenems, or fluoroquinolones, typically for at least three to four weeks and longer if bone involvement is present. Auricular cellulitis is treated with warm compresses and intravenous antibiotics targeting staphylococci and streptococci. Severe perichondritis requires extended antibiotic therapy, often with agents such as piperacillin–tazobactam or nafcillin combined with ciprofloxacin, and may benefit from incision and drainage. Ramsay Hunt syndrome is treated with acyclovir and corticosteroids, and early therapy improves facial nerve outcomes; ophthalmologic evaluation is recommended to assess ocular involvement.
Ongoing Care and Follow-Up
Referral to an otolaryngologist is advised when ear pain persists despite appropriate initial evaluation and management.
Complications
Otitis media can lead to mastoiditis, epidural abscess, dural venous sinus thrombosis, meningitis, or brain abscess. Malignant otitis externa may extend to the cavernous sinus or contralateral petrous apex, and although meningitis and brain abscess are uncommon, they are serious potential sequelae.
Basics
Description
Otalgia denotes pain originating in or perceived in the ear. Evaluation should consider patient age and associated symptoms such as sore throat, fever, headache, visual changes, and symptom duration. A systematic ear examination is essential, beginning with the auricle and external auditory meatus, followed by inspection of the auditory canal and tympanic membrane to guide the differential diagnosis. A complete head and neck examination may uncover lymphadenopathy, pharyngeal or nasal inflammation, thyroid disease, or dental and oral pathology. Cerumen can obstruct visualization of the tympanic membrane and should be gently removed when necessary. Any exudate within the auditory canal should be cultured. Pain elicited by movement of the pinna suggests otitis externa, foreign body, or impacted cerumen. Perichondritis, an infectious process of the outer ear cartilage, must be differentiated from relapsing polychondritis, a noninfectious rheumatologic condition.
Epidemiology
Approximately half of ear pain cases are referred from non-otologic sources. Acute otitis externa, commonly termed swimmer’s ear, occurs more frequently during summer months. Recurrent acute otitis media affects about one-fifth of children. Head and neck malignancies typically occur after age 50 but may present earlier, even without classic risk factors; several forms of nasopharyngeal carcinoma are associated with Epstein–Barr virus infection. Auricular cellulitis often follows minor trauma. Perichondritis usually develops after burns, trauma, or upper-ear piercings and is most commonly caused by Pseudomonas aeruginosa or Staphylococcus aureus. Chronic otitis externa often results from repeated minor trauma such as scratching or cotton swab use, and chronic middle-ear drainage may be mistaken for this condition. Malignant otitis externa is a destructive infection of the external canal and skull base.
Etiology
Ear pain is frequently referred because the ear receives sensory innervation from cranial nerves V, VII, VIII, IX, and X. Referred otalgia may arise from dental disease, gingival abscesses, nasopharyngeal or laryngeal inflammation or tumors, sinusitis, temporomandibular joint disorders, tonsillitis, tongue lesions, cervical spine disease, neural irritation such as trigeminal neuralgia or acoustic neuroma, gastroesophageal reflux in infants, thyroiditis, lateral sinus thrombosis, posterior fossa inflammation, or medication effects. Primary ear pathology causing otalgia includes acute or chronic otitis media, tympanic membrane rupture, anterior canal wall fracture, mastoiditis, Ménière disease, and eustachian tube dysfunction. Malignant otitis externa is almost always due to Pseudomonas aeruginosa. Otalgia may also accompany migraine, atypical facial pain, and herpes simplex infection of cranial nerves V, VII, or IX. Herpes zoster affecting the external auditory canal may produce ipsilateral facial paralysis, known as Ramsay Hunt syndrome, from involvement of the geniculate ganglion. Facial nerve palsy may also occur with Lyme disease. Neoplasms of the infratemporal fossa may present solely with ear pain. Acute otitis externa is most often caused by Pseudomonas aeruginosa, Staphylococcus aureus, or streptococcal species, with swimming and canal trauma as major risk factors.
Diagnosis
Clinical Manifestations
Auricular cellulitis presents with a swollen, erythematous, warm, mildly tender ear. Perichondritis causes marked swelling, redness, heat, and severe tenderness of the pinna with relative sparing of the lobule. Chronic otitis externa more commonly causes itching than pain. Nasopharyngeal carcinoma may be asymptomatic early but often produces unilateral serous otitis media from eustachian tube obstruction, nasal blockage, or epistaxis, and advanced disease may cause cranial nerve palsies, especially involving nerves III, IV, VI, and VII. Malignant otitis externa typically affects elderly patients with diabetes or individuals with HIV and presents with severe otalgia, otorrhea, possible hearing loss, tender pinna, trismus from temporomandibular involvement, and sometimes cranial nerve palsies, most often of nerve VII. Fever and weight loss are uncommon. Examination reveals canal edema, erythema, purulent discharge, debris, and granulation tissue. Vesicular lesions in the external canal suggest herpes zoster and warrant evaluation for facial nerve palsy. Hearing loss with abnormal tympanic membrane findings indicates serous or bacterial otitis media or cholesteatoma. Nasal polyps, marked septal deviation, or nasopharyngeal tumors may be associated with otitis media.
Physical Examination
Findings such as an erythematous canal with discharge, preauricular lymphadenopathy, and pain on tragal or pinna manipulation suggest otitis externa. Fever, irritability in children, and a bulging or erythematous tympanic membrane with loss of the cone of light indicate otitis media, sometimes with canal pus if perforation is present. Altered mental status or meningeal signs such as headache and neck stiffness indicate possible central nervous system involvement and require urgent management.
Diagnostic Tests and Interpretation
Laboratory Studies
Peripheral leukocytosis is uncommon in malignant otitis externa, whereas erythrocyte sedimentation rate is typically elevated. Cerebrospinal fluid analysis may occasionally show pleocytosis and increased protein.
Imaging
Dental pathology can be assessed with panoramic radiography. In malignant otitis externa, CT of the temporal bone or mastoid often demonstrates bony erosion and new bone formation, while MRI more accurately defines soft-tissue extension and skull-base involvement.
Treatment
Medications
Acute otitis externa is managed with careful canal cleaning and topical therapy using antiseptics or antibiotic drops such as polymyxin–neomycin, along with counseling on ear hygiene and water avoidance. Malignant otitis externa requires urgent otolaryngology consultation and prolonged antipseudomonal therapy with agents such as cefepime, ceftazidime, carbapenems, or fluoroquinolones, typically for at least three to four weeks and longer if bone involvement is present. Auricular cellulitis is treated with warm compresses and intravenous antibiotics targeting staphylococci and streptococci. Severe perichondritis requires extended antibiotic therapy, often with agents such as piperacillin–tazobactam or nafcillin combined with ciprofloxacin, and may benefit from incision and drainage. Ramsay Hunt syndrome is treated with acyclovir and corticosteroids, and early therapy improves facial nerve outcomes; ophthalmologic evaluation is recommended to assess ocular involvement.
Ongoing Care and Follow-Up
Referral to an otolaryngologist is advised when ear pain persists despite appropriate initial evaluation and management.
Complications
Otitis media can lead to mastoiditis, epidural abscess, dural venous sinus thrombosis, meningitis, or brain abscess. Malignant otitis externa may extend to the cavernous sinus or contralateral petrous apex, and although meningitis and brain abscess are uncommon, they are serious potential sequelae.
- Published on
Infectious Diseases and Microbiology: Insect Bites and Stings
Basics
Description
Zoonoses are infections transmitted from nonhuman animals to humans, and vectors are the animals responsible for transmission. Insect bites and stings can lead to a wide spectrum of infectious diseases with acute, subacute, or highly variable presentations. Noninfectious reactions such as anaphylaxis and inflammatory responses are also common.
Approach to the Patient
Clinical evaluation requires awareness of geographic distribution, vector life cycles, and characteristic clinical syndromes. A detailed history of mosquito or tick exposure and the timing of bites can help narrow the differential diagnosis. Travel history is critical and should include dates, destinations, stopovers, pretravel medical advice, vaccinations, malaria prophylaxis, and preventive measures such as bed nets or repellents. Laboratory confirmation may support the diagnosis but is often unavailable early in illness. Multiple infections can follow a single exposure, as some vectors transmit more than one pathogen simultaneously. Malaria must always be considered in febrile travelers returning from endemic regions and treated as a medical emergency; given the risk of severe outcomes, empiric antimicrobial therapy is often appropriate when suspicion is high.
Epidemiology
Hundreds of thousands of Lyme disease cases have been reported in the United States, with most occurring in the Northeast, Minnesota, and Wisconsin. Rocky Mountain spotted fever occurs throughout the Americas, predominantly in the southern and southeastern United States, with higher incidence in warmer months. West Nile virus has been present in the US since 1999, with tens of thousands of reported cases; most infections are asymptomatic, and true exposure rates are likely much higher. Eastern equine encephalitis is a rare but severe mosquito-borne viral infection found mainly along the East and Gulf coasts, reported sporadically over decades. Malaria remains an important imported infection, with over a thousand cases reported annually in the US.
General Prevention
In areas with tick exposure, preventive strategies include wearing protective clothing and using proper tick-removal techniques with fine tweezers, avoiding crushing or abrupt removal. Insect repellents containing DEET remain the most effective option, particularly when combined with permethrin-treated clothing. Concentrations of 10–30% DEET provide strong protection; higher concentrations do not significantly increase efficacy. Plant-based repellents such as picaridin, PMD, or citronella have some benefit but are less effective than DEET.
Etiology
In the United States, clinicians may encounter both local and imported vector-borne diseases. Mosquitoes transmit malaria, dengue, West Nile virus, yellow fever, chikungunya, and viral encephalitides including eastern equine encephalitis. Ticks transmit Lyme disease, babesiosis, ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever, tularemia, southern tick–associated rash illness, Bartonella infection, tick paralysis, and other rickettsioses. Flies may transmit bartonellosis, African trypanosomiasis, filariasis, onchocerciasis, leishmaniasis, or cause myiasis. Fleas transmit plague, murine typhus, and tungiasis.
Diagnosis
Incubation periods and symptom patterns vary by pathogen. Falciparum malaria typically incubates for about two weeks and presents with fever, chills, headache, abdominal or neck pain, nausea, vomiting, and sometimes jaundice. West Nile virus incubates for up to two weeks; most cases are asymptomatic, while symptomatic illness usually causes short-lived fever, myalgias, headache, and sometimes rash, with possible neurologic involvement. Colorado tick fever presents after several days with biphasic fever, severe headache, photophobia, and myalgias, occasionally with a transient rash. Dengue usually incubates for several days to two weeks and classically causes fever, retro-orbital headache, rash, and marked muscle and joint pain. bisnes
Nenek dia
Diagnostic Tests and Interpretation
Laboratory evaluation depends on the suspected condition. Blood smears are mandatory in febrile patients returning from malaria-endemic regions. Lyme disease is diagnosed by serology with enzyme immunoassay confirmed by Western blot in compatible cases. Babesiosis is identified on blood smear by intraerythrocytic parasites, with PCR and serology as adjuncts. West Nile virus infection is diagnosed by IgM detection in serum or cerebrospinal fluid. Neuroimaging in eastern equine encephalitis often reveals characteristic thalamic and basal ganglia abnormalities.
Treatment
Management depends on the specific infection and is detailed in disease-specific references. Given the severity of some vector-borne illnesses, prompt empiric therapy is often warranted when clinical suspicion is high.
Ongoing Care and Complications
Eastern equine encephalitis carries a high mortality rate, and many survivors have permanent neurologic disability. Delayed diagnosis and treatment of falciparum malaria significantly increase mortality and the risk of permanent neurologic damage. Lyme disease may involve the nervous system or cardiac conduction pathways, leading to neurologic deficits or arrhythmias. Dengue may cause mucosal bleeding and exacerbate preexisting gastrointestinal lesions. Colorado tick fever has been associated with rare but serious complications including encephalitis, meningitis, hemorrhage, myocarditis, orchitis, atypical pneumonia, and hepatitis.
Basics
Description
Zoonoses are infections transmitted from nonhuman animals to humans, and vectors are the animals responsible for transmission. Insect bites and stings can lead to a wide spectrum of infectious diseases with acute, subacute, or highly variable presentations. Noninfectious reactions such as anaphylaxis and inflammatory responses are also common.
Approach to the Patient
Clinical evaluation requires awareness of geographic distribution, vector life cycles, and characteristic clinical syndromes. A detailed history of mosquito or tick exposure and the timing of bites can help narrow the differential diagnosis. Travel history is critical and should include dates, destinations, stopovers, pretravel medical advice, vaccinations, malaria prophylaxis, and preventive measures such as bed nets or repellents. Laboratory confirmation may support the diagnosis but is often unavailable early in illness. Multiple infections can follow a single exposure, as some vectors transmit more than one pathogen simultaneously. Malaria must always be considered in febrile travelers returning from endemic regions and treated as a medical emergency; given the risk of severe outcomes, empiric antimicrobial therapy is often appropriate when suspicion is high.
Epidemiology
Hundreds of thousands of Lyme disease cases have been reported in the United States, with most occurring in the Northeast, Minnesota, and Wisconsin. Rocky Mountain spotted fever occurs throughout the Americas, predominantly in the southern and southeastern United States, with higher incidence in warmer months. West Nile virus has been present in the US since 1999, with tens of thousands of reported cases; most infections are asymptomatic, and true exposure rates are likely much higher. Eastern equine encephalitis is a rare but severe mosquito-borne viral infection found mainly along the East and Gulf coasts, reported sporadically over decades. Malaria remains an important imported infection, with over a thousand cases reported annually in the US.
General Prevention
In areas with tick exposure, preventive strategies include wearing protective clothing and using proper tick-removal techniques with fine tweezers, avoiding crushing or abrupt removal. Insect repellents containing DEET remain the most effective option, particularly when combined with permethrin-treated clothing. Concentrations of 10–30% DEET provide strong protection; higher concentrations do not significantly increase efficacy. Plant-based repellents such as picaridin, PMD, or citronella have some benefit but are less effective than DEET.
Etiology
In the United States, clinicians may encounter both local and imported vector-borne diseases. Mosquitoes transmit malaria, dengue, West Nile virus, yellow fever, chikungunya, and viral encephalitides including eastern equine encephalitis. Ticks transmit Lyme disease, babesiosis, ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever, tularemia, southern tick–associated rash illness, Bartonella infection, tick paralysis, and other rickettsioses. Flies may transmit bartonellosis, African trypanosomiasis, filariasis, onchocerciasis, leishmaniasis, or cause myiasis. Fleas transmit plague, murine typhus, and tungiasis.
Diagnosis
Incubation periods and symptom patterns vary by pathogen. Falciparum malaria typically incubates for about two weeks and presents with fever, chills, headache, abdominal or neck pain, nausea, vomiting, and sometimes jaundice. West Nile virus incubates for up to two weeks; most cases are asymptomatic, while symptomatic illness usually causes short-lived fever, myalgias, headache, and sometimes rash, with possible neurologic involvement. Colorado tick fever presents after several days with biphasic fever, severe headache, photophobia, and myalgias, occasionally with a transient rash. Dengue usually incubates for several days to two weeks and classically causes fever, retro-orbital headache, rash, and marked muscle and joint pain. bisnes
Nenek dia
Diagnostic Tests and Interpretation
Laboratory evaluation depends on the suspected condition. Blood smears are mandatory in febrile patients returning from malaria-endemic regions. Lyme disease is diagnosed by serology with enzyme immunoassay confirmed by Western blot in compatible cases. Babesiosis is identified on blood smear by intraerythrocytic parasites, with PCR and serology as adjuncts. West Nile virus infection is diagnosed by IgM detection in serum or cerebrospinal fluid. Neuroimaging in eastern equine encephalitis often reveals characteristic thalamic and basal ganglia abnormalities.
Treatment
Management depends on the specific infection and is detailed in disease-specific references. Given the severity of some vector-borne illnesses, prompt empiric therapy is often warranted when clinical suspicion is high.
Ongoing Care and Complications
Eastern equine encephalitis carries a high mortality rate, and many survivors have permanent neurologic disability. Delayed diagnosis and treatment of falciparum malaria significantly increase mortality and the risk of permanent neurologic damage. Lyme disease may involve the nervous system or cardiac conduction pathways, leading to neurologic deficits or arrhythmias. Dengue may cause mucosal bleeding and exacerbate preexisting gastrointestinal lesions. Colorado tick fever has been associated with rare but serious complications including encephalitis, meningitis, hemorrhage, myocarditis, orchitis, atypical pneumonia, and hepatitis.
- Published on
Infectious Diseases and Microbiology: Insect Bites and Stings
Basics
Description
Zoonoses are infections transmitted from nonhuman animals to humans, and vectors are the animals responsible for transmission. Insect bites and stings can lead to a wide spectrum of infectious diseases with acute, subacute, or highly variable presentations. Noninfectious reactions such as anaphylaxis and inflammatory responses are also common.
Approach to the Patient
Clinical evaluation requires awareness of geographic distribution, vector life cycles, and characteristic clinical syndromes. A detailed history of mosquito or tick exposure and the timing of bites can help narrow the differential diagnosis. Travel history is critical and should include dates, destinations, stopovers, pretravel medical advice, vaccinations, malaria prophylaxis, and preventive measures such as bed nets or repellents. Laboratory confirmation may support the diagnosis but is often unavailable early in illness. Multiple infections can follow a single exposure, as some vectors transmit more than one pathogen simultaneously. Malaria must always be considered in febrile travelers returning from endemic regions and treated as a medical emergency; given the risk of severe outcomes, empiric antimicrobial therapy is often appropriate when suspicion is high.
Epidemiology
Hundreds of thousands of Lyme disease cases have been reported in the United States, with most occurring in the Northeast, Minnesota, and Wisconsin. Rocky Mountain spotted fever occurs throughout the Americas, predominantly in the southern and southeastern United States, with higher incidence in warmer months. West Nile virus has been present in the US since 1999, with tens of thousands of reported cases; most infections are asymptomatic, and true exposure rates are likely much higher. Eastern equine encephalitis is a rare but severe mosquito-borne viral infection found mainly along the East and Gulf coasts, reported sporadically over decades. Malaria remains an important imported infection, with over a thousand cases reported annually in the US.
General Prevention
In areas with tick exposure, preventive strategies include wearing protective clothing and using proper tick-removal techniques with fine tweezers, avoiding crushing or abrupt removal. Insect repellents containing DEET remain the most effective option, particularly when combined with permethrin-treated clothing. Concentrations of 10–30% DEET provide strong protection; higher concentrations do not significantly increase efficacy. Plant-based repellents such as picaridin, PMD, or citronella have some benefit but are less effective than DEET.
Etiology
In the United States, clinicians may encounter both local and imported vector-borne diseases. Mosquitoes transmit malaria, dengue, West Nile virus, yellow fever, chikungunya, and viral encephalitides including eastern equine encephalitis. Ticks transmit Lyme disease, babesiosis, ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever, tularemia, southern tick–associated rash illness, Bartonella infection, tick paralysis, and other rickettsioses. Flies may transmit bartonellosis, African trypanosomiasis, filariasis, onchocerciasis, leishmaniasis, or cause myiasis. Fleas transmit plague, murine typhus, and tungiasis.
Diagnosis
Incubation periods and symptom patterns vary by pathogen. Falciparum malaria typically incubates for about two weeks and presents with fever, chills, headache, abdominal or neck pain, nausea, vomiting, and sometimes jaundice. West Nile virus incubates for up to two weeks; most cases are asymptomatic, while symptomatic illness usually causes short-lived fever, myalgias, headache, and sometimes rash, with possible neurologic involvement. Colorado tick fever presents after several days with biphasic fever, severe headache, photophobia, and myalgias, occasionally with a transient rash. Dengue usually incubates for several days to two weeks and classically causes fever, retro-orbital headache, rash, and marked muscle and joint pain.
Diagnostic Tests and Interpretation
Laboratory evaluation depends on the suspected condition. Blood smears are mandatory in febrile patients returning from malaria-endemic regions. Lyme disease is diagnosed by serology with enzyme immunoassay confirmed by Western blot in compatible cases. Babesiosis is identified on blood smear by intraerythrocytic parasites, with PCR and serology as adjuncts. West Nile virus infection is diagnosed by IgM detection in serum or cerebrospinal fluid. Neuroimaging in eastern equine encephalitis often reveals characteristic thalamic and basal ganglia abnormalities.
Treatment
Management depends on the specific infection and is detailed in disease-specific references. Given the severity of some vector-borne illnesses, prompt empiric therapy is often warranted when clinical suspicion is high.
Ongoing Care and Complications
Eastern equine encephalitis carries a high mortality rate, and many survivors have permanent neurologic disability. Delayed diagnosis and treatment of falciparum malaria significantly increase mortality and the risk of permanent neurologic damage. Lyme disease may involve the nervous system or cardiac conduction pathways, leading to neurologic deficits or arrhythmias. Dengue may cause mucosal bleeding and exacerbate preexisting gastrointestinal lesions. Colorado tick fever has been associated with rare but serious complications including encephalitis, meningitis, hemorrhage, myocarditis, orchitis, atypical pneumonia, and hepatitis.
Basics
Description
Zoonoses are infections transmitted from nonhuman animals to humans, and vectors are the animals responsible for transmission. Insect bites and stings can lead to a wide spectrum of infectious diseases with acute, subacute, or highly variable presentations. Noninfectious reactions such as anaphylaxis and inflammatory responses are also common.
Approach to the Patient
Clinical evaluation requires awareness of geographic distribution, vector life cycles, and characteristic clinical syndromes. A detailed history of mosquito or tick exposure and the timing of bites can help narrow the differential diagnosis. Travel history is critical and should include dates, destinations, stopovers, pretravel medical advice, vaccinations, malaria prophylaxis, and preventive measures such as bed nets or repellents. Laboratory confirmation may support the diagnosis but is often unavailable early in illness. Multiple infections can follow a single exposure, as some vectors transmit more than one pathogen simultaneously. Malaria must always be considered in febrile travelers returning from endemic regions and treated as a medical emergency; given the risk of severe outcomes, empiric antimicrobial therapy is often appropriate when suspicion is high.
Epidemiology
Hundreds of thousands of Lyme disease cases have been reported in the United States, with most occurring in the Northeast, Minnesota, and Wisconsin. Rocky Mountain spotted fever occurs throughout the Americas, predominantly in the southern and southeastern United States, with higher incidence in warmer months. West Nile virus has been present in the US since 1999, with tens of thousands of reported cases; most infections are asymptomatic, and true exposure rates are likely much higher. Eastern equine encephalitis is a rare but severe mosquito-borne viral infection found mainly along the East and Gulf coasts, reported sporadically over decades. Malaria remains an important imported infection, with over a thousand cases reported annually in the US.
General Prevention
In areas with tick exposure, preventive strategies include wearing protective clothing and using proper tick-removal techniques with fine tweezers, avoiding crushing or abrupt removal. Insect repellents containing DEET remain the most effective option, particularly when combined with permethrin-treated clothing. Concentrations of 10–30% DEET provide strong protection; higher concentrations do not significantly increase efficacy. Plant-based repellents such as picaridin, PMD, or citronella have some benefit but are less effective than DEET.
Etiology
In the United States, clinicians may encounter both local and imported vector-borne diseases. Mosquitoes transmit malaria, dengue, West Nile virus, yellow fever, chikungunya, and viral encephalitides including eastern equine encephalitis. Ticks transmit Lyme disease, babesiosis, ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever, tularemia, southern tick–associated rash illness, Bartonella infection, tick paralysis, and other rickettsioses. Flies may transmit bartonellosis, African trypanosomiasis, filariasis, onchocerciasis, leishmaniasis, or cause myiasis. Fleas transmit plague, murine typhus, and tungiasis.
Diagnosis
Incubation periods and symptom patterns vary by pathogen. Falciparum malaria typically incubates for about two weeks and presents with fever, chills, headache, abdominal or neck pain, nausea, vomiting, and sometimes jaundice. West Nile virus incubates for up to two weeks; most cases are asymptomatic, while symptomatic illness usually causes short-lived fever, myalgias, headache, and sometimes rash, with possible neurologic involvement. Colorado tick fever presents after several days with biphasic fever, severe headache, photophobia, and myalgias, occasionally with a transient rash. Dengue usually incubates for several days to two weeks and classically causes fever, retro-orbital headache, rash, and marked muscle and joint pain.
Diagnostic Tests and Interpretation
Laboratory evaluation depends on the suspected condition. Blood smears are mandatory in febrile patients returning from malaria-endemic regions. Lyme disease is diagnosed by serology with enzyme immunoassay confirmed by Western blot in compatible cases. Babesiosis is identified on blood smear by intraerythrocytic parasites, with PCR and serology as adjuncts. West Nile virus infection is diagnosed by IgM detection in serum or cerebrospinal fluid. Neuroimaging in eastern equine encephalitis often reveals characteristic thalamic and basal ganglia abnormalities.
Treatment
Management depends on the specific infection and is detailed in disease-specific references. Given the severity of some vector-borne illnesses, prompt empiric therapy is often warranted when clinical suspicion is high.
Ongoing Care and Complications
Eastern equine encephalitis carries a high mortality rate, and many survivors have permanent neurologic disability. Delayed diagnosis and treatment of falciparum malaria significantly increase mortality and the risk of permanent neurologic damage. Lyme disease may involve the nervous system or cardiac conduction pathways, leading to neurologic deficits or arrhythmias. Dengue may cause mucosal bleeding and exacerbate preexisting gastrointestinal lesions. Colorado tick fever has been associated with rare but serious complications including encephalitis, meningitis, hemorrhage, myocarditis, orchitis, atypical pneumonia, and hepatitis.
- Published on
Infectious Diseases and Microbiology: Hepatosplenomegaly and Fever
Basics
Description
A midclavicular liver span of at least 12.5 cm supports hepatomegaly. Splenomegaly is defined as a spleen exceeding 250 g or one that is palpable, and on ultrasound is suggested by a cephalocaudal length of 13 cm or more
.
Approach to the Patient
Evaluating Hepatomegaly
Palpate to identify the lower liver edge at the right midclavicular line, then use gentle percussion to define the upper border so liver span can be measured; a span ≥12.5 cm supports hepatomegaly. Because hyperinflated lungs can push the liver downward, the upper border must be assessed to avoid overcalling enlargement.
Evaluating Splenomegaly
Bedside assessment should include both palpation and percussion. Palpation is best done bimanually with the patient supine and in the right lateral position. Percussion methods by Nixon and Castell provide the best diagnostic performance. In Nixon’s method, the patient lies on the right side and percussion begins in the posterior axillary line at the level where lung resonance ends, moving obliquely toward the left anterior costal margin; a dullness span over 8 cm suggests splenomegaly and has moderate sensitivity with high specificity. In Castell’s method, the patient is supine and percussion in the lowest intercostal space at the left anterior axillary line should remain resonant during inspiration if the spleen is normal; this approach has moderate sensitivity and specificity. If missing splenomegaly would change management, confirm with ultrasound or scintigraphy.
Evaluating Fever with Liver and/or Spleen Enlargement
Obtain a comprehensive history emphasizing travel and immigration, occupation, sexual history, intravenous drug use, animal exposure, and family history of malignancy, connective tissue disease, or inherited conditions. Look for associated findings including jaundice, fever duration and pattern, lymphadenopathy, rashes or bite exposures, liver edge texture and tenderness, an enlarged gallbladder or other abdominal mass, and spleen size and consistency. Initial testing commonly includes broad laboratory evaluation, heterophile antibody testing, hepatitis studies, imaging, and in selected cases bone marrow evaluation, endoscopy, and/or liver biopsy.
Epidemiology
In young adults, palpability of the liver and spleen can occur even without disease. In a large sample of healthy military personnel, the liver was not palpable or only at the costal margin in over half, and descended only 1–2 cm below the margin in many others. Studies of healthy college entrants have found a small proportion with unexplained palpable spleens, and palpable spleens have been reported in a notable minority of otherwise normal postpartum women.
Etiology
Hepatomegaly with Fever
Infectious causes include pyogenic or amoebic abscess, ascending cholangitis, chronic granulomatous disease, chronic Q fever, ehrlichiosis, histoplasmosis, HIV, infectious hepatitis, infectious mononucleosis, leptospirosis, syphilis, tuberculosis, and parasitic infections. Malignant causes include diffuse primary hepatic cancer, diffuse metastases, myeloproliferative disorders, lymphoma, and angiosarcoma. Inflammatory causes include sarcoidosis, autoimmune hepatitis, familial Mediterranean fever, and Still’s disease.
Splenomegaly with Fever
Infectious causes include viral infections such as hepatitis, infectious mononucleosis, and HIV; bacterial infections such as endocarditis, pyogenic abscess, salmonellosis, leptospirosis, brucellosis, Bartonella; fungal infections such as histoplasmosis; mycobacterial infections including miliary tuberculosis and nontuberculous mycobacteria; and parasitic infections including malaria, toxoplasmosis, amoebic liver abscess, schistosomiasis with Katayama fever, visceral leishmaniasis, babesiosis, and ehrlichiosis. Inflammatory causes include rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, and hemophagocytic lymphohistiocytosis. Malignant causes include lymphoma, acute and chronic leukemias, and myelodysplastic or myeloproliferative syndromes. Numerous parasites can enlarge liver and spleen depending on exposure context, including malaria, schistosomiasis, hydatid disease, leishmaniasis, toxocariasis, toxoplasmosis, liver flukes such as Fasciola hepatica, and echinococcal cysts, which can enlarge organs but are rarely febrile. Fever occurs in roughly half of toxoplasmosis and toxocariasis cases.
Diagnosis
History and Clinical Manifestations
In young adults, the combination of fatigue, sore throat, fever, lymphadenopathy, and hepatosplenomegaly is most often infectious mononucleosis. Fever with abdominal pain that may localize to the right upper quadrant, vomiting or anorexia, hepatomegaly, leukocytosis with elevated sedimentation rate, and otherwise unexplained anemia should raise concern for liver abscess. Pyogenic liver abscess most often arises from biliary disease and is commonly due to enteric organisms including Escherichia coli, Klebsiella, enterococci, anginosus group streptococci, and anaerobes, and is most often seen in adults in their fifth and sixth decades. Pyogenic liver abscess with metastatic infection such as endophthalmitis, meningitis, or other focal abscesses suggests Klebsiella pneumoniae, particularly in patients with diabetes and those from East Asia. Amoebic liver abscess is now most often seen in travelers and migrants; men have markedly higher risk of invasive Entamoeba histolytica disease including liver abscess, gastrointestinal symptoms such as nausea, vomiting, or diarrhea occur in a minority, and presentation may occur years after exposure. In HIV with advanced immunosuppression, fever with lymphadenopathy and splenomegaly is often mycobacterial, but lymphoma must be ruled out. Leptospirosis should be considered with compatible exposures and fever with rigors, headache, and myalgias, with severe disease involving pulmonary, hepatic, and renal dysfunction, aseptic meningitis, and bleeding tendencies. In tropical settings, splenomegaly may reflect hyper-reactive malarial splenomegaly, characterized by fever, anemia, weight loss, abdominal discomfort, lassitude, abnormal liver tests, elevated IgM, and hepatic sinusoidal lymphocytosis.
Physical Examination
Beyond confirming fever and organ enlargement, search for diagnostic clues such as lymphadenopathy suggesting lymphoma, infectious mononucleosis, brucellosis, schistosomiasis, HIV, or mycobacterial infection; rashes suggesting schistosomiasis, rickettsial disease, leishmaniasis, mononucleosis, Still’s disease, or syphilis; pharyngeal findings supporting mononucleosis; murmurs or embolic phenomena supporting endocarditis, Bartonella, or brucellosis; jaundice supporting viral hepatitis, cholangitis, or leptospirosis; conjunctival suffusion supporting leptospirosis; and joint findings supporting rheumatoid arthritis, lupus, or Still’s disease.
Diagnostic Tests and Interpretation
Laboratory Studies
Leukocytosis with a left shift supports bacterial infection. Marked lymphocytosis with atypical lymphocytes on smear supports infectious mononucleosis and can be confirmed early with heterophile antibody testing or with EBV viral capsid antigen IgM. Eosinophilia can accompany certain parasitic causes of hepatosplenomegaly but is not typical of amoebic infection. Three sets of blood cultures off antibiotics help exclude most endocarditis, while Bartonella, Brucella, and Q fever are better assessed by serology. Based on exposure history, obtain HIV, syphilis, and viral hepatitis testing, and consider serologies for rickettsial disease, Entamoeba, toxoplasma, schistosomiasis, Q fever, Fasciola, leptospirosis, and ehrlichiosis, along with blood films for malaria and babesiosis. Include biochemistry, autoimmune markers, and ferritin when inflammatory disease is considered. If imaging identifies an abscess, image-guided aspiration can establish diagnosis. Excisional lymph node biopsy or liver biopsy offers the highest yield for lymphoma. Bone marrow biopsy or splenic aspirate can diagnose leishmaniasis, with PCR or serology as alternatives.
Imaging
Ultrasound can confirm enlargement and identify causes such as abscess, hepatocellular carcinoma, or biliary pathology. Contrast-enhanced CT is helpful when ultrasound is nondiagnostic and suspicion remains for focal lesions or lymphoma. MRI is rarely needed but may help distinguish abscess from malignancy.
Treatment
Medications
Therapy is directed by the underlying diagnosis. Confirmed liver abscess requires antibiotics targeting likely organisms; pyogenic abscess is generally managed with percutaneous drainage plus antibiotics, with surgery reserved for failed drainage or complex multiloculated disease. Praziquantel is effective for Schistosoma mansoni in advanced hepatosplenic disease and is preferred when Schistosoma haematobium coinfection is present. Fascioliasis is typically treated with triclabendazole 10 mg/kg for one to two days; bithionol is an alternative, and the role of praziquantel is uncertain.
Ongoing Care and Follow-Up
Advise patients with splenomegaly to avoid contact sports and monitor for spontaneous rupture, which almost always presents with severe upper abdominal pain that often starts in the left upper quadrant, spreads more diffusely, and can radiate to the left shoulder.
Complications
In the United States, spontaneous splenic rupture is most commonly associated with infectious mononucleosis. Although rare, occurring in a small fraction of mononucleosis cases, it is the leading cause of death related to infectious mononucleosis.
Basics
Description
A midclavicular liver span of at least 12.5 cm supports hepatomegaly. Splenomegaly is defined as a spleen exceeding 250 g or one that is palpable, and on ultrasound is suggested by a cephalocaudal length of 13 cm or more
.
Approach to the Patient
Evaluating Hepatomegaly
Palpate to identify the lower liver edge at the right midclavicular line, then use gentle percussion to define the upper border so liver span can be measured; a span ≥12.5 cm supports hepatomegaly. Because hyperinflated lungs can push the liver downward, the upper border must be assessed to avoid overcalling enlargement.
Evaluating Splenomegaly
Bedside assessment should include both palpation and percussion. Palpation is best done bimanually with the patient supine and in the right lateral position. Percussion methods by Nixon and Castell provide the best diagnostic performance. In Nixon’s method, the patient lies on the right side and percussion begins in the posterior axillary line at the level where lung resonance ends, moving obliquely toward the left anterior costal margin; a dullness span over 8 cm suggests splenomegaly and has moderate sensitivity with high specificity. In Castell’s method, the patient is supine and percussion in the lowest intercostal space at the left anterior axillary line should remain resonant during inspiration if the spleen is normal; this approach has moderate sensitivity and specificity. If missing splenomegaly would change management, confirm with ultrasound or scintigraphy.
Evaluating Fever with Liver and/or Spleen Enlargement
Obtain a comprehensive history emphasizing travel and immigration, occupation, sexual history, intravenous drug use, animal exposure, and family history of malignancy, connective tissue disease, or inherited conditions. Look for associated findings including jaundice, fever duration and pattern, lymphadenopathy, rashes or bite exposures, liver edge texture and tenderness, an enlarged gallbladder or other abdominal mass, and spleen size and consistency. Initial testing commonly includes broad laboratory evaluation, heterophile antibody testing, hepatitis studies, imaging, and in selected cases bone marrow evaluation, endoscopy, and/or liver biopsy.
Epidemiology
In young adults, palpability of the liver and spleen can occur even without disease. In a large sample of healthy military personnel, the liver was not palpable or only at the costal margin in over half, and descended only 1–2 cm below the margin in many others. Studies of healthy college entrants have found a small proportion with unexplained palpable spleens, and palpable spleens have been reported in a notable minority of otherwise normal postpartum women.
Etiology
Hepatomegaly with Fever
Infectious causes include pyogenic or amoebic abscess, ascending cholangitis, chronic granulomatous disease, chronic Q fever, ehrlichiosis, histoplasmosis, HIV, infectious hepatitis, infectious mononucleosis, leptospirosis, syphilis, tuberculosis, and parasitic infections. Malignant causes include diffuse primary hepatic cancer, diffuse metastases, myeloproliferative disorders, lymphoma, and angiosarcoma. Inflammatory causes include sarcoidosis, autoimmune hepatitis, familial Mediterranean fever, and Still’s disease.
Splenomegaly with Fever
Infectious causes include viral infections such as hepatitis, infectious mononucleosis, and HIV; bacterial infections such as endocarditis, pyogenic abscess, salmonellosis, leptospirosis, brucellosis, Bartonella; fungal infections such as histoplasmosis; mycobacterial infections including miliary tuberculosis and nontuberculous mycobacteria; and parasitic infections including malaria, toxoplasmosis, amoebic liver abscess, schistosomiasis with Katayama fever, visceral leishmaniasis, babesiosis, and ehrlichiosis. Inflammatory causes include rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, and hemophagocytic lymphohistiocytosis. Malignant causes include lymphoma, acute and chronic leukemias, and myelodysplastic or myeloproliferative syndromes. Numerous parasites can enlarge liver and spleen depending on exposure context, including malaria, schistosomiasis, hydatid disease, leishmaniasis, toxocariasis, toxoplasmosis, liver flukes such as Fasciola hepatica, and echinococcal cysts, which can enlarge organs but are rarely febrile. Fever occurs in roughly half of toxoplasmosis and toxocariasis cases.
Diagnosis
History and Clinical Manifestations
In young adults, the combination of fatigue, sore throat, fever, lymphadenopathy, and hepatosplenomegaly is most often infectious mononucleosis. Fever with abdominal pain that may localize to the right upper quadrant, vomiting or anorexia, hepatomegaly, leukocytosis with elevated sedimentation rate, and otherwise unexplained anemia should raise concern for liver abscess. Pyogenic liver abscess most often arises from biliary disease and is commonly due to enteric organisms including Escherichia coli, Klebsiella, enterococci, anginosus group streptococci, and anaerobes, and is most often seen in adults in their fifth and sixth decades. Pyogenic liver abscess with metastatic infection such as endophthalmitis, meningitis, or other focal abscesses suggests Klebsiella pneumoniae, particularly in patients with diabetes and those from East Asia. Amoebic liver abscess is now most often seen in travelers and migrants; men have markedly higher risk of invasive Entamoeba histolytica disease including liver abscess, gastrointestinal symptoms such as nausea, vomiting, or diarrhea occur in a minority, and presentation may occur years after exposure. In HIV with advanced immunosuppression, fever with lymphadenopathy and splenomegaly is often mycobacterial, but lymphoma must be ruled out. Leptospirosis should be considered with compatible exposures and fever with rigors, headache, and myalgias, with severe disease involving pulmonary, hepatic, and renal dysfunction, aseptic meningitis, and bleeding tendencies. In tropical settings, splenomegaly may reflect hyper-reactive malarial splenomegaly, characterized by fever, anemia, weight loss, abdominal discomfort, lassitude, abnormal liver tests, elevated IgM, and hepatic sinusoidal lymphocytosis.
Physical Examination
Beyond confirming fever and organ enlargement, search for diagnostic clues such as lymphadenopathy suggesting lymphoma, infectious mononucleosis, brucellosis, schistosomiasis, HIV, or mycobacterial infection; rashes suggesting schistosomiasis, rickettsial disease, leishmaniasis, mononucleosis, Still’s disease, or syphilis; pharyngeal findings supporting mononucleosis; murmurs or embolic phenomena supporting endocarditis, Bartonella, or brucellosis; jaundice supporting viral hepatitis, cholangitis, or leptospirosis; conjunctival suffusion supporting leptospirosis; and joint findings supporting rheumatoid arthritis, lupus, or Still’s disease.
Diagnostic Tests and Interpretation
Laboratory Studies
Leukocytosis with a left shift supports bacterial infection. Marked lymphocytosis with atypical lymphocytes on smear supports infectious mononucleosis and can be confirmed early with heterophile antibody testing or with EBV viral capsid antigen IgM. Eosinophilia can accompany certain parasitic causes of hepatosplenomegaly but is not typical of amoebic infection. Three sets of blood cultures off antibiotics help exclude most endocarditis, while Bartonella, Brucella, and Q fever are better assessed by serology. Based on exposure history, obtain HIV, syphilis, and viral hepatitis testing, and consider serologies for rickettsial disease, Entamoeba, toxoplasma, schistosomiasis, Q fever, Fasciola, leptospirosis, and ehrlichiosis, along with blood films for malaria and babesiosis. Include biochemistry, autoimmune markers, and ferritin when inflammatory disease is considered. If imaging identifies an abscess, image-guided aspiration can establish diagnosis. Excisional lymph node biopsy or liver biopsy offers the highest yield for lymphoma. Bone marrow biopsy or splenic aspirate can diagnose leishmaniasis, with PCR or serology as alternatives.
Imaging
Ultrasound can confirm enlargement and identify causes such as abscess, hepatocellular carcinoma, or biliary pathology. Contrast-enhanced CT is helpful when ultrasound is nondiagnostic and suspicion remains for focal lesions or lymphoma. MRI is rarely needed but may help distinguish abscess from malignancy.
Treatment
Medications
Therapy is directed by the underlying diagnosis. Confirmed liver abscess requires antibiotics targeting likely organisms; pyogenic abscess is generally managed with percutaneous drainage plus antibiotics, with surgery reserved for failed drainage or complex multiloculated disease. Praziquantel is effective for Schistosoma mansoni in advanced hepatosplenic disease and is preferred when Schistosoma haematobium coinfection is present. Fascioliasis is typically treated with triclabendazole 10 mg/kg for one to two days; bithionol is an alternative, and the role of praziquantel is uncertain.
Ongoing Care and Follow-Up
Advise patients with splenomegaly to avoid contact sports and monitor for spontaneous rupture, which almost always presents with severe upper abdominal pain that often starts in the left upper quadrant, spreads more diffusely, and can radiate to the left shoulder.
Complications
In the United States, spontaneous splenic rupture is most commonly associated with infectious mononucleosis. Although rare, occurring in a small fraction of mononucleosis cases, it is the leading cause of death related to infectious mononucleosis.
- Published on
Infectious Diseases and Microbiology: Gonorrhea
Basics
Description
Gonorrhea is caused by Neisseria gonorrhoeae, a gram-negative intracellular diplococcus that infects humans only. Spread occurs through direct mucosal inoculation during sexual contact or childbirth. Transmission is more efficient from men to women, and a single sexual exposure can infect up to half of female partners.
Epidemiology
Gonorrhea remains a major global public health issue and contributes substantially to morbidity, especially in developing regions. Worldwide incidence has been estimated at roughly 62 million new infections annually, with highest rates in sub-Saharan Africa, South and Southeast Asia, the Caribbean, and Latin America. In the United States, hundreds of thousands of cases were reported in 2008 with the highest rates in females aged 15–19 and males aged 20–24; reported rates were higher in African American and Hispanic populations than in White populations.
Risk Factors
Risk is increased by female sex, age under 25, prior gonorrhea or other STIs, new or multiple partners, inconsistent condom use, commercial sex work, drug use, and travel to high-prevalence countries.
General Prevention
Control relies on early detection, immediate treatment at diagnosis, and treatment of sexual partners. Partners within 60 days before symptom onset should be evaluated and treated. Delaying sexual debut, reducing partner number, and consistent condom use decrease transmission.
Etiology
Disease is due to N. gonorrhoeae, a nonmotile, non–spore-forming gram-negative diplococcus.
Commonly Associated Conditions
Coinfection with other STIs is common; Chlamydia coinfection occurs in about one-third of cases. Gonorrhea also increases susceptibility to acquiring HIV.
Diagnosis
Clinical manifestations depend on infection site, bacterial strain, host factors, sex, and coinfections. Many infections are asymptomatic in both sexes. Incubation is typically 2–7 days. In men, urethritis usually begins with dysuria followed by purulent discharge, and acute epididymitis is the most frequent complication. In women, urethritis can cause dysuria, frequency, and urgency, and cervicitis may develop with purulent discharge, cramping, dyspareunia, and postcoital or intermenstrual bleeding; symptoms often intensify around menstruation. Untreated infection can ascend, causing pelvic inflammatory disease with infertility and chronic pelvic pain. Conjunctivitis usually results from autoinoculation and can rapidly threaten vision. In neonates, infection is commonly ophthalmia neonatorum acquired during delivery; ocular prophylaxis with agents such as silver nitrate drops or tetracycline ointment is used for prevention. Disseminated gonococcal infection may present with fever, rash, tenosynovitis, and septic arthritis and can resemble an influenza-like illness without obvious mucosal symptoms, so urethral/cervical, rectal, and pharyngeal sites should be sampled.
Diagnostic Tests and Interpretation
Laboratory Studies
In symptomatic men, Gram stain of urethral discharge can show polymorphonuclear cells and gram-negative intracellular diplococci, but Gram stain performs poorly with endocervical, rectal, and pharyngeal specimens. Culture allows antimicrobial susceptibility testing and should be performed on selective media such as modified Thayer–Martin (or equivalent) with aerobic conditions and increased CO₂; rapid processing is essential because gonococci do not tolerate drying. Strains linked to dissemination may be more fastidious and harder to grow. Nucleic acid–based tests can detect N. gonorrhoeae from swabs or urine with sensitivity and specificity comparable or better than culture, but cost is higher and cross-reactivity with nonpathogenic Neisseria species can occur.
Differential Diagnosis
Urethritis can be nongonococcal due to Chlamydia, Ureaplasma, Mycoplasma genitalium, Haemophilus vaginalis, HSV, adenovirus, and others. Vaginal symptoms may reflect candidiasis, bacterial vaginosis, trichomoniasis, or noninfectious etiologies such as chemical irritation, allergy, fistula, or pregnancy-related leukorrhea. Disseminated gonococcal infection must be distinguished from meningococcemia, ecthyma gangrenosum, other bacteremias, septic arthritis from other bacteria, and reactive arthritis.
Treatment
Medications
CDC-recommended therapy has centered on cephalosporins. For uncomplicated urethral, cervical, or rectal infection, recommended single-dose options include ceftriaxone 125 mg IM, cefixime 400 mg PO, or spectinomycin 2 g IM. Pharyngeal infection is harder to eradicate and is treated with ceftriaxone 125 mg IM as the preferred regimen. Gonococcal conjunctivitis is treated with ceftriaxone 125 mg IM once, with saline eye irrigation as an optional adjunct. Disseminated infection is treated with parenteral cephalosporin-based regimens such as ceftriaxone 1 g IM/IV daily or cefotaxime/ceftizoxime 1 g IV three times daily, or spectinomycin 2 g IM twice daily; continue parenteral therapy for 24–48 hours after clinical improvement, then transition to an oral agent such as cefixime 400 mg PO twice daily to complete a total of one week. If chlamydial infection has not been excluded, provide concurrent chlamydia therapy. Fluoroquinolones are not recommended as first-line therapy in the United States because of widespread resistance.
Additional Treatment
Because Chlamydia coinfection is common, initial management should cover chlamydia (e.g., azithromycin or doxycycline) unless it has been ruled out.
Ongoing Care and Follow-Up
Patient Monitoring
A routine test-of-cure is not required after treating uncomplicated infection. If symptoms persist, obtain culture with susceptibility testing; the most common reason for apparent treatment failure is reinfection from an untreated partner.
Patient Education
Advise consistent condom use and provide instruction on correct condom use.
Complications
The most important complication is pelvic inflammatory disease from ascending infection, which can lead to tubo-ovarian abscess, pelvic peritonitis, and Fitz-Hugh–Curtis syndrome, with long-term infertility and chronic pelvic pain. In men, complications include epididymitis, periurethritis, balanitis, acute or chronic prostatitis, orchitis, seminal vasculitis, and infection of Tyson and Cowper glands. Disseminated gonococcemia is more common in women, with menstruation increasing risk, and typically causes tenosynovitis, migratory arthritis, and peripheral skin lesions that may be maculopapular or pustular; blood cultures are positive in only a minority of cases. Endocarditis and meningitis are rare in the antibiotic era.
Basics
Description
Gonorrhea is caused by Neisseria gonorrhoeae, a gram-negative intracellular diplococcus that infects humans only. Spread occurs through direct mucosal inoculation during sexual contact or childbirth. Transmission is more efficient from men to women, and a single sexual exposure can infect up to half of female partners.
Epidemiology
Gonorrhea remains a major global public health issue and contributes substantially to morbidity, especially in developing regions. Worldwide incidence has been estimated at roughly 62 million new infections annually, with highest rates in sub-Saharan Africa, South and Southeast Asia, the Caribbean, and Latin America. In the United States, hundreds of thousands of cases were reported in 2008 with the highest rates in females aged 15–19 and males aged 20–24; reported rates were higher in African American and Hispanic populations than in White populations.
Risk Factors
Risk is increased by female sex, age under 25, prior gonorrhea or other STIs, new or multiple partners, inconsistent condom use, commercial sex work, drug use, and travel to high-prevalence countries.
General Prevention
Control relies on early detection, immediate treatment at diagnosis, and treatment of sexual partners. Partners within 60 days before symptom onset should be evaluated and treated. Delaying sexual debut, reducing partner number, and consistent condom use decrease transmission.
Etiology
Disease is due to N. gonorrhoeae, a nonmotile, non–spore-forming gram-negative diplococcus.
Commonly Associated Conditions
Coinfection with other STIs is common; Chlamydia coinfection occurs in about one-third of cases. Gonorrhea also increases susceptibility to acquiring HIV.
Diagnosis
Clinical manifestations depend on infection site, bacterial strain, host factors, sex, and coinfections. Many infections are asymptomatic in both sexes. Incubation is typically 2–7 days. In men, urethritis usually begins with dysuria followed by purulent discharge, and acute epididymitis is the most frequent complication. In women, urethritis can cause dysuria, frequency, and urgency, and cervicitis may develop with purulent discharge, cramping, dyspareunia, and postcoital or intermenstrual bleeding; symptoms often intensify around menstruation. Untreated infection can ascend, causing pelvic inflammatory disease with infertility and chronic pelvic pain. Conjunctivitis usually results from autoinoculation and can rapidly threaten vision. In neonates, infection is commonly ophthalmia neonatorum acquired during delivery; ocular prophylaxis with agents such as silver nitrate drops or tetracycline ointment is used for prevention. Disseminated gonococcal infection may present with fever, rash, tenosynovitis, and septic arthritis and can resemble an influenza-like illness without obvious mucosal symptoms, so urethral/cervical, rectal, and pharyngeal sites should be sampled.
Diagnostic Tests and Interpretation
Laboratory Studies
In symptomatic men, Gram stain of urethral discharge can show polymorphonuclear cells and gram-negative intracellular diplococci, but Gram stain performs poorly with endocervical, rectal, and pharyngeal specimens. Culture allows antimicrobial susceptibility testing and should be performed on selective media such as modified Thayer–Martin (or equivalent) with aerobic conditions and increased CO₂; rapid processing is essential because gonococci do not tolerate drying. Strains linked to dissemination may be more fastidious and harder to grow. Nucleic acid–based tests can detect N. gonorrhoeae from swabs or urine with sensitivity and specificity comparable or better than culture, but cost is higher and cross-reactivity with nonpathogenic Neisseria species can occur.
Differential Diagnosis
Urethritis can be nongonococcal due to Chlamydia, Ureaplasma, Mycoplasma genitalium, Haemophilus vaginalis, HSV, adenovirus, and others. Vaginal symptoms may reflect candidiasis, bacterial vaginosis, trichomoniasis, or noninfectious etiologies such as chemical irritation, allergy, fistula, or pregnancy-related leukorrhea. Disseminated gonococcal infection must be distinguished from meningococcemia, ecthyma gangrenosum, other bacteremias, septic arthritis from other bacteria, and reactive arthritis.
Treatment
Medications
CDC-recommended therapy has centered on cephalosporins. For uncomplicated urethral, cervical, or rectal infection, recommended single-dose options include ceftriaxone 125 mg IM, cefixime 400 mg PO, or spectinomycin 2 g IM. Pharyngeal infection is harder to eradicate and is treated with ceftriaxone 125 mg IM as the preferred regimen. Gonococcal conjunctivitis is treated with ceftriaxone 125 mg IM once, with saline eye irrigation as an optional adjunct. Disseminated infection is treated with parenteral cephalosporin-based regimens such as ceftriaxone 1 g IM/IV daily or cefotaxime/ceftizoxime 1 g IV three times daily, or spectinomycin 2 g IM twice daily; continue parenteral therapy for 24–48 hours after clinical improvement, then transition to an oral agent such as cefixime 400 mg PO twice daily to complete a total of one week. If chlamydial infection has not been excluded, provide concurrent chlamydia therapy. Fluoroquinolones are not recommended as first-line therapy in the United States because of widespread resistance.
Additional Treatment
Because Chlamydia coinfection is common, initial management should cover chlamydia (e.g., azithromycin or doxycycline) unless it has been ruled out.
Ongoing Care and Follow-Up
Patient Monitoring
A routine test-of-cure is not required after treating uncomplicated infection. If symptoms persist, obtain culture with susceptibility testing; the most common reason for apparent treatment failure is reinfection from an untreated partner.
Patient Education
Advise consistent condom use and provide instruction on correct condom use.
Complications
The most important complication is pelvic inflammatory disease from ascending infection, which can lead to tubo-ovarian abscess, pelvic peritonitis, and Fitz-Hugh–Curtis syndrome, with long-term infertility and chronic pelvic pain. In men, complications include epididymitis, periurethritis, balanitis, acute or chronic prostatitis, orchitis, seminal vasculitis, and infection of Tyson and Cowper glands. Disseminated gonococcemia is more common in women, with menstruation increasing risk, and typically causes tenosynovitis, migratory arthritis, and peripheral skin lesions that may be maculopapular or pustular; blood cultures are positive in only a minority of cases. Endocarditis and meningitis are rare in the antibiotic era.
- Published on
Emergency and Acute Medicine – Lymphadenopathy and Fever
Overview and Definitions
Lymphadenitis refers to inflammation of one or more lymph nodes, while lymphangitis involves inflammation of lymphatic channels; both may occur in acute or chronic disease. Mesenteric lymphadenitis results from inflammation of mesenteric nodes and may clinically mimic acute appendicitis. In most regions, lymph nodes larger than 1 cm are abnormal; epitrochlear nodes greater than 0.5 cm and inguinal nodes greater than 1.5–2 cm are considered enlarged, although palpable inguinal nodes are common in healthy adults. Generalized lymphadenopathy is defined as involvement of two or more noncontiguous nodal regions.
Clinical Approach
Fever commonly accompanies lymphadenopathy, with infection being the leading cause. Lymph node enlargement may be incidental or the primary presenting feature, and clinicians must determine whether observation or further investigation is required. A detailed history and comprehensive physical examination are essential. Duration is informative, as suppurative infections usually present within one week, whereas chronic lymphadenopathy suggests infections such as HIV or tuberculosis, malignancy, inflammatory, or autoimmune disease. Epidemiologic factors including travel, sick contacts, and animal exposure should be assessed. Associated symptoms include weight loss, fever, night sweats, sore throat, cough, pruritus, fatigue, lymph node pain, and myalgia or arthralgia. Examination should include all nodal regions to determine whether disease is localized or generalized, along with abdominal assessment for hepatosplenomegaly. Findings such as anemia, petechiae, or bleeding suggest bone marrow infiltration. While many infections cause fever with lymphadenopathy, pathogens such as Francisella tularensis, Bartonella henselae, and mycobacteria often present with a single prominent lymph node and fever.
Epidemiology
More than two-thirds of patients presenting to primary care with lymphadenopathy have nonspecific or upper respiratory causes. The likelihood of malignancy increases with age, particularly over 50 years. In primary care, approximately 1% of patients with lymphadenopathy have an underlying malignancy. Acute mesenteric lymphadenitis is more common in children. In developed countries, mycobacterial lymphadenopathy is more often due to nontuberculous species.
Etiology
Infectious causes include viral infections such as Epstein–Barr virus, cytomegalovirus, herpes simplex virus, dengue, rubella, measles, HIV, and West Nile virus; bacterial infections including streptococci, Staphylococcus aureus, Bartonella henselae, brucellosis, tularemia, plague, melioidosis, tuberculosis, nontuberculous mycobacteria, listeriosis, leptospirosis, secondary syphilis, diphtheria, typhoid fever, and lymphogranuloma venereum; fungal infections such as histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, and cryptococcosis; parasitic infections including toxoplasmosis, leishmaniasis, trypanosomiasis, and filariasis; and rickettsial diseases. Immunologic causes include systemic lupus erythematosus, rheumatoid arthritis, vasculitides, Still’s disease, dermatomyositis, graft-versus-host disease, juvenile idiopathic arthritis, mixed connective tissue disease, serum sickness, and Sjögren’s syndrome. Malignant causes include Hodgkin and non-Hodgkin lymphomas, acute and chronic leukemias, hairy cell leukemia, amyloidosis, sarcomas, and metastatic disease. Other causes include lipid storage disorders, endocrine diseases such as hyperthyroidism and Addison disease, Castleman disease, Kikuchi disease, drug reactions, familial Mediterranean fever, and Kawasaki disease. In HIV infection, lymphadenopathy ranges from early follicular hyperplasia to opportunistic infections and malignancies, with common causes including lymphoma, mycobacterial infection, toxoplasmosis, systemic fungal infection, and bacillary angiomatosis.
Diagnostic Evaluation
Assessment of lymph nodes should document size, shape, consistency, mobility, and tenderness. Hard nodes suggest carcinoma, rubbery firm non-tender nodes are typical of lymphoma, and tender mobile nodes usually indicate reactive infection. Some malignancies, such as acute leukemia, may cause rapid enlargement with pain. Initial laboratory evaluation should be guided by risk factors and may include blood cultures, HIV testing, syphilis serology, heterophile antibody testing, toxoplasma, CMV, EBV serologies, Bartonella serology, urine histoplasma antigen, autoimmune markers, and other targeted tests. Fine-needle aspiration can be useful, but excisional biopsy provides superior diagnostic yield, particularly for lymphoma. Lymph node specimens should be evaluated with cultures, mycobacterial and fungal stains, cytology, and molecular diagnostics. Chest radiography may reveal pulmonary or mediastinal involvement. Ultrasonography is useful for superficial nodes, while CT or MRI better evaluate deep nodal disease and guide biopsy. PET imaging identifies metabolically active nodes. In the absence of high-risk features, observation for 2–4 weeks is appropriate, with biopsy indicated if lymphadenopathy persists.
Management
Treatment depends on the underlying etiology and should be directed at the identified cause. Empiric therapy may be required in severe infection, while malignancy or autoimmune disease requires disease-specific management.
Follow-Up and Prognosis
In patients without features concerning for malignancy or severe infection, clinical observation for 2–4 weeks after initial evaluation is appropriate before proceeding to biopsy.
Complications
Delayed diagnosis or treatment of infectious lymphadenopathy may lead to disseminated or severe infection.
Overview and Definitions
Lymphadenitis refers to inflammation of one or more lymph nodes, while lymphangitis involves inflammation of lymphatic channels; both may occur in acute or chronic disease. Mesenteric lymphadenitis results from inflammation of mesenteric nodes and may clinically mimic acute appendicitis. In most regions, lymph nodes larger than 1 cm are abnormal; epitrochlear nodes greater than 0.5 cm and inguinal nodes greater than 1.5–2 cm are considered enlarged, although palpable inguinal nodes are common in healthy adults. Generalized lymphadenopathy is defined as involvement of two or more noncontiguous nodal regions.
Clinical Approach
Fever commonly accompanies lymphadenopathy, with infection being the leading cause. Lymph node enlargement may be incidental or the primary presenting feature, and clinicians must determine whether observation or further investigation is required. A detailed history and comprehensive physical examination are essential. Duration is informative, as suppurative infections usually present within one week, whereas chronic lymphadenopathy suggests infections such as HIV or tuberculosis, malignancy, inflammatory, or autoimmune disease. Epidemiologic factors including travel, sick contacts, and animal exposure should be assessed. Associated symptoms include weight loss, fever, night sweats, sore throat, cough, pruritus, fatigue, lymph node pain, and myalgia or arthralgia. Examination should include all nodal regions to determine whether disease is localized or generalized, along with abdominal assessment for hepatosplenomegaly. Findings such as anemia, petechiae, or bleeding suggest bone marrow infiltration. While many infections cause fever with lymphadenopathy, pathogens such as Francisella tularensis, Bartonella henselae, and mycobacteria often present with a single prominent lymph node and fever.
Epidemiology
More than two-thirds of patients presenting to primary care with lymphadenopathy have nonspecific or upper respiratory causes. The likelihood of malignancy increases with age, particularly over 50 years. In primary care, approximately 1% of patients with lymphadenopathy have an underlying malignancy. Acute mesenteric lymphadenitis is more common in children. In developed countries, mycobacterial lymphadenopathy is more often due to nontuberculous species.
Etiology
Infectious causes include viral infections such as Epstein–Barr virus, cytomegalovirus, herpes simplex virus, dengue, rubella, measles, HIV, and West Nile virus; bacterial infections including streptococci, Staphylococcus aureus, Bartonella henselae, brucellosis, tularemia, plague, melioidosis, tuberculosis, nontuberculous mycobacteria, listeriosis, leptospirosis, secondary syphilis, diphtheria, typhoid fever, and lymphogranuloma venereum; fungal infections such as histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, and cryptococcosis; parasitic infections including toxoplasmosis, leishmaniasis, trypanosomiasis, and filariasis; and rickettsial diseases. Immunologic causes include systemic lupus erythematosus, rheumatoid arthritis, vasculitides, Still’s disease, dermatomyositis, graft-versus-host disease, juvenile idiopathic arthritis, mixed connective tissue disease, serum sickness, and Sjögren’s syndrome. Malignant causes include Hodgkin and non-Hodgkin lymphomas, acute and chronic leukemias, hairy cell leukemia, amyloidosis, sarcomas, and metastatic disease. Other causes include lipid storage disorders, endocrine diseases such as hyperthyroidism and Addison disease, Castleman disease, Kikuchi disease, drug reactions, familial Mediterranean fever, and Kawasaki disease. In HIV infection, lymphadenopathy ranges from early follicular hyperplasia to opportunistic infections and malignancies, with common causes including lymphoma, mycobacterial infection, toxoplasmosis, systemic fungal infection, and bacillary angiomatosis.
Diagnostic Evaluation
Assessment of lymph nodes should document size, shape, consistency, mobility, and tenderness. Hard nodes suggest carcinoma, rubbery firm non-tender nodes are typical of lymphoma, and tender mobile nodes usually indicate reactive infection. Some malignancies, such as acute leukemia, may cause rapid enlargement with pain. Initial laboratory evaluation should be guided by risk factors and may include blood cultures, HIV testing, syphilis serology, heterophile antibody testing, toxoplasma, CMV, EBV serologies, Bartonella serology, urine histoplasma antigen, autoimmune markers, and other targeted tests. Fine-needle aspiration can be useful, but excisional biopsy provides superior diagnostic yield, particularly for lymphoma. Lymph node specimens should be evaluated with cultures, mycobacterial and fungal stains, cytology, and molecular diagnostics. Chest radiography may reveal pulmonary or mediastinal involvement. Ultrasonography is useful for superficial nodes, while CT or MRI better evaluate deep nodal disease and guide biopsy. PET imaging identifies metabolically active nodes. In the absence of high-risk features, observation for 2–4 weeks is appropriate, with biopsy indicated if lymphadenopathy persists.
Management
Treatment depends on the underlying etiology and should be directed at the identified cause. Empiric therapy may be required in severe infection, while malignancy or autoimmune disease requires disease-specific management.
Follow-Up and Prognosis
In patients without features concerning for malignancy or severe infection, clinical observation for 2–4 weeks after initial evaluation is appropriate before proceeding to biopsy.
Complications
Delayed diagnosis or treatment of infectious lymphadenopathy may lead to disseminated or severe infection.
- Published on
Emergency and Acute Medicine – Lung Nodules
Overview and Definitions
Pulmonary nodules are rounded opacities surrounded by lung parenchyma and are typically less than 3–4 cm in diameter; larger lesions are classified as lung masses. Pathologically, a pulmonary nodule is a small, approximately spherical, circumscribed focus of abnormal tissue, while radiologically it is defined as a round opacity, at least moderately well marginated, and no more than 3 cm in maximum diameter. Linear or planar opacities are not considered nodules. Chest imaging may reveal a solitary pulmonary nodule, often referred to as a coin lesion, or multiple pulmonary nodules.
Clinical Approach
The primary objective is to distinguish benign from malignant nodules. Evaluation begins with a thorough history, as the probability of malignancy increases with age and is rare in patients younger than 35 years. Important malignancy risk factors include prior lung cancer, family history of lung cancer, cigarette smoking, second-hand smoke exposure, occupational carcinogen exposure such as asbestos or radon, pulmonary fibrosis, chronic obstructive pulmonary disease, and alpha-1 antitrypsin deficiency. A higher cumulative smoking burden is associated with increased cancer risk. If malignancy is suspected, it is essential to determine whether the lesion represents a primary lung cancer or metastatic disease. Fever suggests an infectious etiology, and immunocompromised patients are at risk for opportunistic infections presenting as solitary or multiple nodules. Physical examination may reveal signs of malignancy including cachexia, anemia, jaundice, clubbing, bone pain, abdominal masses, or superior vena cava syndrome. Radiologic features such as size, distribution, shape, calcification pattern, cavitation, lymphadenopathy, pleural effusion, and clustering provide diagnostic clues. Low-risk nodules may be followed with serial CT imaging, whereas larger or suspicious nodules warrant biopsy, PET imaging, or video-assisted thoracoscopic surgery. Empiric antimicrobial therapy should be initiated in immunocompromised patients or those at risk for rapid deterioration.
Epidemiology
Pulmonary nodules are common, with up to 51% of smokers aged 50 years or older having nodules detected on CT. Fewer than 1% of nodules smaller than 5 mm are malignant in patients without a history of cancer. The likelihood of malignancy increases with size: approximately 0.2% for nodules under 3 mm, 0.9% for 4–7 mm, 18% for 8–20 mm, and greater than 50% for nodules larger than 20 mm. Male smokers have a tenfold increased risk of lung cancer compared with nonsmokers, rising to 15–35 times higher in heavy smokers. Paragonimus westermani infection can present as a lung nodule in endemic regions of East and Southeast Asia. Tuberculosis commonly presents with hilar lymphadenopathy, and histoplasmosis is the most frequent cause of hospitalization from endemic mycoses in the United States.
Etiology and Pathophysiology
Solitary pulmonary nodules may be caused by primary lung malignancies including adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and small cell carcinoma, as well as metastatic disease from breast, head and neck, thyroid, melanoma, colon, kidney, sarcoma, and germ cell tumors. Other causes include carcinoid tumors, infections such as bacterial abscesses, tuberculosis, atypical mycobacteria, histoplasmosis, blastomycosis, coccidioidomycosis, cryptococcosis, aspergilloma, nocardiosis, Pneumocystis infection, and parasitic infections including echinococcosis, dirofilariasis, ascariasis, and paragonimiasis. Benign neoplasms include hamartoma, lipoma, and fibroma. Non-neoplastic causes include arteriovenous malformations, bronchogenic cysts, granulomatosis with polyangiitis, sarcoidosis, rheumatoid nodules, amyloidoma, rounded atelectasis, intrapulmonary lymph nodes, hematoma, pulmonary infarction, and mucoid impaction. Multiple pulmonary nodules are more often benign when less than 1 cm, but in patients with known malignancy, nodules larger than 0.5 cm are more likely metastatic. Infectious causes of multiple nodules include septic emboli, fungal infections, tuberculosis, atypical mycobacteria, and paragonimiasis, while inflammatory conditions such as sarcoidosis, rheumatoid arthritis, and vasculitis are also common causes.
Diagnostic Evaluation
History should assess for tuberculosis risk factors, immunosuppression, aspiration risk, and exposure to endemic fungi. Lung abscesses may arise from aspiration, tricuspid valve endocarditis, or septic thrombophlebitis such as Lemierre syndrome, often in patients with poor dentition or prolonged recumbency. Symptoms include cough, sputum production, dyspnea, fever, night sweats, weight loss, and anorexia. Laboratory evaluation may include blood cultures, sputum Gram stain and culture, fungal cultures, acid-fast bacilli staining and mycobacterial cultures, cryptococcal antigen testing, galactomannan and beta-D-glucan assays, and serologic testing for endemic fungi. Imaging with high-resolution CT can detect nodules as small as 1–2 mm. Benign calcification patterns include homogeneous, central, concentric, and popcorn calcifications, while malignant features include eccentric or amorphous calcification and spiculated borders. Ground-glass halos suggest invasive fungal infection, particularly aspergillosis. PET imaging identifies metabolically active lesions. Transthoracic echocardiography is indicated when septic emboli are suspected, and CT of the neck should be performed if Lemierre syndrome is considered. Percutaneous biopsy or VATS is indicated when malignancy risk is high.
Management
Empiric antibiotics should be initiated in patients with fever or systemic toxicity after obtaining blood cultures. Suspected tuberculosis requires differentiation between latent and active disease using clinical assessment, imaging, and sputum studies. Mild pulmonary histoplasmosis may not require treatment, but persistent or moderate-to-severe disease is treated with itraconazole or amphotericin B followed by itraconazole. Lung abscesses are typically polymicrobial and treated with beta-lactam/beta-lactamase inhibitors or clindamycin. Voriconazole is first-line therapy for invasive aspergillosis, with surgical debridement considered when feasible. Paragonimiasis is treated with praziquantel or triclabendazole.
Follow-Up and Prognosis
Malignant solitary pulmonary nodules typically double in volume over 20–400 days. Low-risk nodules smaller than 1 cm may be monitored with serial CT imaging, while high-risk nodules should be surgically excised. PET scanning is most useful for nodules larger than 1 cm with intermediate malignancy risk to guide management decisions.
Complications
Untreated lung abscesses may progress to respiratory failure requiring mechanical ventilation. Cavitation may occur in infectious, malignant, and inflammatory nodules, and cavitary lesions are frequently complicated by secondary Aspergillus infection.
