Infectious Disease and Microbiology – Toxic shock syndrome

Toxic shock syndrome (TSS) is a severe toxin-mediated illness caused mainly by Staphylococcus aureus or Streptococcus pyogenes. It typically presents with abrupt fever, hypotension, diffuse erythematous rash, and rapidly progressive multiorgan dysfunction. Gastrointestinal symptoms, severe myalgias, mucosal hyperemia, renal or hepatic dysfunction, thrombocytopenia, and altered mental status may occur, while desquamation of the palms and soles often develops during convalescence.

Epidemiology

Staphylococcal TSS is uncommon, with an estimated incidence of roughly 1–3 cases per 100,000 people, whereas streptococcal TSS is also rare but generally carries a higher mortality.

Approximately half of staphylococcal TSS cases have historically occurred in menstruating women using tampons, although nonmenstrual disease occurs in people of all ages and sexes.

Streptococcal TSS most often accompanies invasive soft-tissue infection, particularly necrotizing fasciitis, myonecrosis, or severe cellulitis.

Risk factors

Important risk factors for staphylococcal TSS include tampon use, barrier contraceptive devices, postpartum infection, septic abortion, gynecologic procedures, surgical wounds, burns, nasal packing, skin infections, bacteremia, and musculoskeletal infections.

Risk factors for streptococcal TSS include minor trauma, open wounds, surgery, varicella, invasive group A streptococcal infection, and close contact with a person who has invasive streptococcal disease.

Pathophysiology

TSS is caused by bacterial toxins that act as superantigens.

These toxins bypass conventional antigen processing and directly activate large populations of T lymphocytes, producing massive release of inflammatory cytokines such as tumor necrosis factor, interleukin-1, and interleukin-6.

The resulting cytokine surge causes high fever, profound vasodilation, capillary leakage, hypotension, shock, and tissue injury.

In menstrual staphylococcal TSS, tampons can provide a local environment that promotes colonization and toxin production by S. aureus.

Etiology

Most cases of staphylococcal TSS are associated with S. aureus strains producing toxic shock syndrome toxin-1 (TSST-1).

Other staphylococcal enterotoxins can occasionally produce a similar syndrome.

For disease to develop, the patient generally must be colonized or infected with a toxigenic strain and lack sufficient neutralizing antibodies against its toxin.

Streptococcal TSS is caused by invasive Streptococcus pyogenes infection, with production of streptococcal pyrogenic exotoxins and other virulence factors.

Clinical presentation

TSS develops rapidly over hours to a few days.

Patients usually present with high fever, hypotension, diffuse erythematous rash, vomiting, diarrhea, severe myalgia, weakness, and signs of multiorgan involvement.

Shock can progress rapidly and may require substantial fluid resuscitation and vasopressor support.

Staphylococcal toxic shock syndrome

The classic presentation includes a temperature of at least approximately 38.9°C, diffuse macular erythroderma, and hypotension.

At least several organ systems are usually involved.

Gastrointestinal manifestations commonly include vomiting and diarrhea at the onset of illness.

Muscle involvement is characterized by severe myalgia or elevated creatine kinase.

Mucosal involvement can produce conjunctival, oral, pharyngeal, or vaginal hyperemia.

Renal involvement may present with elevated creatinine or pyuria, while hepatic involvement causes elevated bilirubin or aminotransferases.

Thrombocytopenia is common.

Neurologic manifestations may include confusion or disorientation without focal neurologic signs.

A diffuse “sunburn-like” rash is characteristic, followed approximately one to two weeks later by desquamation, particularly of the palms and soles.

An obvious focus of infection is often absent in staphylococcal TSS.

Streptococcal toxic shock syndrome

Streptococcal TSS is usually associated with a clear invasive focus such as necrotizing fasciitis, myositis, cellulitis, or another deep soft-tissue infection.

Diagnosis is supported by identification of group A streptococcus from a sterile or clinically relevant site together with hypotension and evidence of multiorgan dysfunction.

Organ involvement may include acute kidney injury, coagulopathy or DIC, hepatic injury, acute respiratory distress syndrome, generalized erythematous rash, and soft-tissue necrosis.

Bacteremia occurs much more frequently in streptococcal TSS than in staphylococcal TSS.

Physical examination

The most prominent finding in staphylococcal TSS is often a diffuse erythematous macular rash.

Desquamation is a delayed finding and usually does not help with the earliest diagnosis.

In menstruating patients with possible TSS, a gynecologic examination is important, and any tampon or vaginal foreign body should be removed immediately.

Patients with streptococcal TSS should be carefully examined for a source of invasive infection, including painful swollen soft tissues, bullae, skin discoloration, crepitus, rapidly spreading erythema, or pain out of proportion to visible findings.

Laboratory findings

Laboratory abnormalities reflect systemic inflammation and multiorgan injury.

Common findings include leukocytosis or leukopenia with a left shift, thrombocytopenia, azotemia, elevated creatine kinase, hypoalbuminemia, hypocalcemia, hypophosphatemia, pyuria, elevated liver enzymes, and metabolic abnormalities associated with shock.

Blood cultures should be obtained in all suspected cases to evaluate for bacteremia and alternative causes such as meningococcemia or gram-negative sepsis.

Blood cultures are often negative in staphylococcal TSS but are positive in a substantial proportion of streptococcal TSS cases.

Cultures should also be obtained from any suspected wound, soft-tissue infection, vaginal source, surgical site, or other focus.

Differential diagnosis

Important alternatives include meningococcemia, severe gram-negative sepsis, Rocky Mountain spotted fever, leptospirosis, measles, Kawasaki disease, heat stroke, severe drug reactions, and other causes of distributive shock with rash.

Necrotizing soft-tissue infection must be considered particularly when the patient has severe focal pain, rapidly progressive swelling, tissue necrosis, or crepitus.

Initial treatment

TSS is a medical emergency requiring immediate resuscitation, broad antimicrobial therapy, and urgent source control.

Treatment should not be delayed while waiting for definitive culture results.

Staphylococcal TSS treatment

Empiric treatment should cover MRSA and suppress toxin production.

A typical initial regimen includes vancomycin plus clindamycin.

Clindamycin is especially valuable because it suppresses bacterial protein synthesis and therefore decreases toxin production.

If cultures identify methicillin-susceptible S. aureus, therapy can be narrowed to an antistaphylococcal β-lactam such as nafcillin or oxacillin, while continuing clindamycin during the acute toxin-mediated phase.

Linezolid is another potential toxin-suppressing anti-MRSA agent in selected cases.

Streptococcal TSS treatment

The preferred regimen is high-dose intravenous penicillin G plus clindamycin.

Penicillin provides potent bactericidal activity against group A streptococcus, while clindamycin reduces toxin synthesis and remains active even when bacterial burden is high.

Antimicrobial treatment is subsequently adjusted according to microbiology, clinical response, and the extent of associated infection.

Source control

Source control is essential and should occur as early as possible.

Any tampon, vaginal device, nasal packing, infected catheter, or other foreign material should be removed.

Abscesses should be drained.

Patients with necrotizing fasciitis or myonecrosis require immediate surgical exploration and aggressive debridement, often with repeated operations.

Delay in surgical treatment of invasive streptococcal infection significantly worsens outcome.

Hemodynamic support

Most patients require admission to the intensive care unit.

Large-volume isotonic intravenous fluid resuscitation is frequently necessary because profound capillary leakage and vasodilation can cause severe intravascular depletion.

If hypotension persists despite fluids, vasopressors are required.

Respiratory support, including mechanical ventilation, may be necessary in patients with ARDS or severe shock.

Intravenous immunoglobulin

IVIG may be considered in severe streptococcal TSS, particularly when shock or invasive soft-tissue disease is refractory to standard therapy.

Its proposed benefit comes from neutralization of circulating exotoxins and superantigens.

Evidence is less certain for staphylococcal TSS, although IVIG may occasionally be considered in exceptionally severe cases.

Routine corticosteroid treatment is not established for TSS.

In-patient considerations

Patients with suspected TSS should be treated in the ICU because deterioration can occur rapidly.

Continuous monitoring of blood pressure, urine output, oxygenation, renal function, hepatic function, platelet count, coagulation parameters, and metabolic status is required.

Discharge is appropriate only after the patient is afebrile, hemodynamically stable without vasopressors, clinically improving, and no longer requires intensive supportive therapy.

Follow-up

Patients recovering from staphylococcal TSS may benefit from evaluation for S. aureus colonization.

In selected patients with persistent nasal carriage, intranasal mupirocin and other decolonization measures may be considered.

Staphylococcal TSS can recur, particularly when the patient remains colonized with a toxin-producing strain and does not develop protective antibodies.

Women who have experienced menstrual TSS should generally avoid tampons and certain intravaginal barrier contraceptive devices, particularly if the risk of recurrence remains high.

Household contacts of patients with invasive streptococcal TSS do not routinely require prophylaxis, although prophylaxis may be considered for particularly vulnerable close contacts such as older adults or those with significant immunocompromise.

Prognosis

Staphylococcal TSS generally has a lower mortality than streptococcal TSS when recognized and treated promptly.

Most deaths occur early and are related to refractory shock and multiorgan failure.

Streptococcal TSS has a substantially worse prognosis because it is often accompanied by bacteremia and destructive invasive soft-tissue infection.

Complications

TSS can cause profound shock with secondary injury to virtually every organ system.

Major complications include acute respiratory distress syndrome, acute kidney injury, disseminated intravascular coagulation, hepatic dysfunction, encephalopathy, myocardial dysfunction, ischemic injury, and multiorgan failure.

Severe invasive streptococcal disease can additionally result in extensive tissue necrosis, limb loss, and death.

High-Yield Pattern

Fever + diffuse sunburn-like rash + hypotension + multiorgan dysfunction → suspect toxic shock syndrome

Menstruating patient using tampon + shock + erythroderma → strongly consider staphylococcal TSS

Severe soft-tissue pain + hypotension + organ failure → suspect streptococcal TSS and necrotizing infection

Staphylococcal TSS → vancomycin + clindamycin initially

Streptococcal TSS → penicillin G + clindamycin

Any TSS → immediate source control + aggressive fluids + vasopressors when needed

Necrotizing soft-tissue infection → urgent surgical exploration and debridement

Click here to start customizing

Infectious Disease and Microbiology – Thrombophlebitis

Suppurative, or septic, thrombophlebitis is an infectious inflammation of a vein accompanied by thrombus formation and bacteremia. It may involve superficial veins, central veins including pelvic veins, intracranial venous structures, or the portal venous system.

Septic thrombophlebitis occasionally complicates central venous catheter-associated bloodstream infection, including infections related to peripherally inserted central catheters (PICC lines).

Epidemiology

Superficial suppurative thrombophlebitis is an important healthcare-associated infection and is usually related to skin and soft-tissue infection or an indwelling intravenous catheter.

Risk increases when peripheral intravenous catheters remain in place for prolonged periods, particularly for three days or longer.

Lower-extremity intravenous catheters are associated with a greater risk than upper-extremity cannulation.

Patients with extensive burns are particularly vulnerable, followed by those with malignancy or receiving systemic corticosteroids.

Septic pelvic thrombophlebitis is uncommon but is primarily associated with pregnancy, cesarean delivery, gynecologic surgery, or septic abortion.

Pelvic septic thrombophlebitis generally develops approximately one to two weeks after delivery or pelvic surgery.

Risk factors

Important risk factors for septic pelvic thrombophlebitis include cesarean delivery, pregnancy, pelvic infection, induced abortion, pelvic surgery, uterine fibroids, malignancy, and hormonal stimulation.

For catheter-associated disease, prolonged venous cannulation, burns, immunosuppression, malignancy, and contamination of the catheter or infusion system increase the likelihood of infection.

Prevention

Avoiding unnecessary venous catheterization and using meticulous sterile technique are fundamental preventive measures.

When possible, lower-extremity peripheral cannulation should be avoided, particularly in patients at increased risk of bloodstream infection.

Catheter insertion sites should be managed using appropriate skin antisepsis and aseptic technique, and unnecessary intravascular catheters should be removed promptly.

Antimicrobial-impregnated central venous catheters may be considered in selected patients or units with persistently high catheter-related infection rates despite strict adherence to standard infection-control practices.

Maximal sterile barrier precautions during central venous catheter insertion remain an important component of prevention.

Pathophysiology

Septic thrombophlebitis develops when a venous thrombus becomes infected, creating a protected nidus in which microorganisms can persist despite the host immune response.

Microorganisms may reach the vein by migration from the skin along a catheter tract, contamination of intravenous fluids or catheter equipment, or hematogenous spread from another infected focus.

The infected thrombus can continuously release organisms into the bloodstream, resulting in persistent or recurrent bacteremia.

Septic pelvic thrombophlebitis

Pelvic thrombophlebitis commonly affects the ovarian veins or inferior vena cava.

Pregnancy and the postpartum state promote venous thrombosis through venous stasis and physiologic hypercoagulability.

Bacteria from vaginal or perineal flora may subsequently infect the thrombus.

Common organisms include Bacteroides species, streptococci, and Enterobacteriaceae such as Escherichia coli.

Portal vein septic thrombophlebitis

Infection and thrombosis of the portal venous system, sometimes called pylephlebitis, may develop secondary to intra-abdominal infection.

It can be associated with hepatic abscesses, although an obvious extrahepatic source is not always found.

Intracranial suppurative thrombophlebitis

Intracranial septic thrombophlebitis may involve cerebral veins or the major dural venous sinuses.

It may occur after infections involving the paranasal sinuses, middle ear, mastoid, facial skin, or oropharynx.

It can also complicate epidural abscess, subdural empyema, bacterial meningitis, or hematogenous dissemination from a distant infectious focus.

Cavernous sinus thrombosis

Septic cavernous sinus thrombosis most commonly develops after paranasal sinusitis or infections involving the face, nose, teeth, or oral cavity.

Staphylococcus aureus is the most important pathogen and is responsible for the majority of septic cavernous sinus thrombosis cases.

Other possible organisms include streptococci, pneumococci, gram-negative bacilli, and anaerobes such as Bacteroides.

In immunocompromised patients or in the appropriate clinical setting, invasive fungi including Aspergillus, Mucor, and Rhizopus should also be considered.

Etiology of superficial disease

The most commonly isolated pathogen in superficial suppurative thrombophlebitis is Staphylococcus aureus.

Other organisms include coagulase-negative staphylococci, Enterobacteriaceae, Pseudomonas aeruginosa, enterococci, and Candida species.

Anaerobic organisms are considerably less common in superficial catheter-associated infections.

Clinical presentation

Fever occurs in most patients with septic thrombophlebitis, although shaking chills or rigors may be absent.

Patients with infection of the large central thoracic veins often present primarily with bacteremia or sepsis and may have few or no local findings.

Persistent bloodstream infection despite appropriate antimicrobial therapy should raise suspicion for an infected intravascular thrombus.

Superficial thrombophlebitis

Superficial septic thrombophlebitis usually produces recognizable local findings.

The affected vein may demonstrate erythema, warmth, tenderness, induration, and lymphangitic spread.

Local findings may be difficult to appreciate in patients with extensive burns or severely abnormal skin.

Pelvic septic thrombophlebitis

Patients commonly present with persistent high fever, chills, anorexia, nausea, vomiting, and lower abdominal or flank discomfort.

Pelvic thrombophlebitis should be considered when postpartum or postoperative fever persists despite apparently appropriate treatment for pelvic infection.

Intracranial thrombophlebitis

Clinical manifestations vary according to the affected venous structure and extent of intracranial involvement.

Patients may develop headache, seizures, focal neurologic deficits, altered consciousness, or manifestations of increased intracranial pressure.

Cavernous sinus thrombosis

Typical symptoms include fever, severe headache, and swelling around the eye.

Patients may also develop diplopia, photophobia, tearing, drowsiness, or changes in mental status.

Physical findings can include periorbital edema, chemosis, proptosis, ptosis, papilledema, and weakness of the extraocular muscles.

An early and particularly important neurologic sign is lateral gaze palsy, reflecting involvement of the abducens nerve.

Diagnosis

Diagnosis requires recognition of the combination of infection, venous thrombosis, and persistent bacteremia or local suppuration.

Blood cultures should be obtained before antimicrobial therapy whenever possible.

Superficial suppurative thrombophlebitis is frequently accompanied by bacteremia, making multiple blood cultures essential.

Routine laboratory studies may include a complete blood count, C-reactive protein, and erythrocyte sedimentation rate.

Persistent leukocytosis or inflammatory marker elevation can support the diagnosis but is nonspecific.

Imaging

Contrast-enhanced CT is particularly useful for detecting septic thrombosis of major central veins, pelvic veins, and the portal venous system.

CT can demonstrate venous filling defects, surrounding inflammatory changes, abscess formation, and extension of infection.

MRI, often combined with MR venography, is preferred when intracranial septic thrombophlebitis is suspected.

Venography can occasionally provide additional evidence of thrombosis in large thoracic central veins.

Catheter-associated infection

When an indwelling venous catheter is suspected as the source, the catheter should generally be removed promptly.

The catheter tip may be sent for microbiologic culture when clinically appropriate.

Persistent bacteremia after catheter removal increases concern for septic thrombosis, endocarditis, or another metastatic focus of infection.

Treatment of superficial septic thrombophlebitis

Prompt antimicrobial treatment is required because untreated disease may progress to sepsis, metastatic infection, or death.

Empiric therapy should cover S. aureus, including MRSA when appropriate.

Vancomycin is commonly used empirically when MRSA is a concern.

In burn patients, immunocompromised individuals, or patients at high risk for gram-negative infection, additional coverage against gram-negative bacilli including Pseudomonas aeruginosa may be necessary.

Antimicrobial treatment should subsequently be narrowed according to blood, catheter, or tissue culture results.

Surgical treatment

Most superficial infections respond to catheter removal and appropriate antimicrobial therapy.

Excision of the infected vein may be required if persistent bacteremia, suppuration, or sepsis continues despite adequate antibiotic therapy and source control.

Treatment of septic pelvic thrombophlebitis

Treatment requires broad-spectrum intravenous antibiotics directed against gram-negative organisms, streptococci, and anaerobes.

Appropriate regimens may include a broad-spectrum β-lactam/β-lactamase inhibitor, a carbapenem, or a cephalosporin combined with anaerobic coverage, depending on local resistance patterns and patient factors.

Anticoagulation with heparin has historically been used in some patients, but its role is not universal and should be individualized according to the clinical situation.

Treatment of intracranial septic thrombophlebitis

Intracranial disease requires urgent high-dose intravenous antimicrobial therapy covering staphylococci, streptococci, gram-negative organisms when appropriate, and anaerobes according to the suspected source.

Vancomycin should be included when MRSA is possible.

Treatment should also aggressively address the primary infectious focus, such as sinusitis, mastoiditis, dental infection, or intracranial abscess.

The role of anticoagulation in septic intracranial thrombophlebitis remains controversial and generally requires individualized assessment involving infectious disease, neurology, neurosurgery, and hematology expertise.

Follow-up

Patients with suppurative thrombophlebitis require close follow-up because relapse can occur if infected thrombus remains.

Repeat blood cultures are important to document clearance of bacteremia.

In selected severe cases, surveillance cultures after completion of therapy may be considered when recurrent bloodstream infection is a major concern.

Patients with unexplained bacteremia, particularly those with burns or recent intravenous catheterization, should have previous catheter sites and cannulated veins carefully examined.

Complications

The infected thrombus may serve as a source of continuous or intermittent bacteremia, leading to sepsis and septic shock.

Metastatic infection may produce pneumonia, septic pulmonary emboli, distant abscesses, or acute bacterial endocarditis.

Intracranial disease can produce cerebral infarction, seizures, meningitis, brain abscess, cranial nerve deficits, or increased intracranial pressure.

High-Yield Pattern

Peripheral IV site + erythema/tenderness + bacteremia → suspect superficial septic thrombophlebitis

Persistent bacteremia after catheter removal → consider septic central venous thrombosis

Postpartum fever despite antibiotics + pelvic or flank pain → consider septic pelvic thrombophlebitis

Sinus/facial infection + fever + proptosis/ophthalmoplegia → suspect septic cavernous sinus thrombosis

Diagnosis → blood cultures + contrast vascular imaging

Treatment → remove infected catheter/source + prolonged targeted IV antibiotics ± drainage or vein excision

Persistent infection despite therapy → search for endocarditis, abscess, or residual infected thrombus

Infectious Disease and Microbiology – Syphilis

Syphilis is a sexually transmitted infection caused by Treponema pallidum. The disease progresses through overlapping stages known as primary, secondary, latent, and tertiary syphilis, while neurosyphilis can occur at any stage.

Epidemiology

Syphilis occurs worldwide and remains an important sexually transmitted infection. Rates are particularly high in populations with increased sexual exposure risk, including people with multiple or anonymous partners.

Coinfection with HIV is relatively common because syphilis and HIV can facilitate the acquisition and transmission of one another.

Risk factors

Important risk factors include unprotected sexual activity, multiple sexual partners, anonymous sexual encounters, injection-drug use, and exchanging sex for money or drugs.

Prevention

Prevention is based on safer sexual practices, including appropriate use of barrier protection during vaginal, anal, and oral sexual contact.

Testing and treatment of infected individuals and their sexual partners are also essential for interrupting transmission.

Pathophysiology

Syphilis is transmitted primarily through direct contact with infectious mucocutaneous lesions, which are most commonly present during primary and secondary disease.

Transmission may occur through sexual contact, kissing, or direct contact with an infectious lesion.

After penetrating the skin or mucous membranes, T. pallidum enters the lymphatic system and bloodstream, allowing widespread dissemination throughout the body.

Vertical transmission across the placenta can cause congenital syphilis.

Transmission through blood products is possible but is now extremely uncommon.

Primary syphilis

Primary syphilis usually appears after an incubation period of approximately 2–4 weeks.

The characteristic lesion is a chancre, which begins as a small papule at the inoculation site and subsequently erodes into a firm, well-defined ulcer.

The classic chancre is painless, indurated, and nonpurulent.

It may occur on the external genitalia, anus, lips, oral cavity, breasts, fingers, or other sites exposed during transmission.

Regional lymphadenopathy may accompany the lesion.

Secondary syphilis

Secondary syphilis develops after systemic dissemination of the organism, usually several weeks after the primary lesion appears or resolves.

Patients may develop fever, malaise, headache, sore throat, weight loss, myalgias, and arthralgias.

A generalized rash occurs in most patients.

The eruption often begins as faint pink macules on the trunk and proximal extremities and later becomes more prominent and papular.

A particularly important clue is involvement of the palms and soles.

The rash is generally nonpruritic and may be macular, papular, maculopapular, or occasionally pustular.

Generalized painless lymphadenopathy is common.

Mucous patches may develop in the mouth and other mucosal surfaces.

Condylomata lata are broad, moist, flat or exophytic lesions occurring particularly in warm intertriginous or perianal regions. These lesions contain large numbers of organisms and are highly infectious.

Other manifestations may include patchy alopecia, loss of eyebrows or beard hair, hepatitis, arthritis, osteitis, periosteitis, gastrointestinal involvement, and immune-complex glomerulonephritis.

Latent syphilis

After secondary manifestations resolve, patients enter the latent stage, during which they have no clinical signs or symptoms but remain serologically positive.

Early latent disease refers to infection acquired relatively recently and carries a greater chance of relapse or transmission than late latent infection.

Late latent syphilis refers to infection of longer duration, during which sexual transmission becomes much less likely.

When the timing of infection cannot be established, the condition is classified as latent syphilis of unknown duration.

Tertiary syphilis

Tertiary disease may develop years or decades after untreated infection.

Cardiovascular manifestations include syphilitic aortitis, particularly involving the ascending aorta, which can lead to aortic aneurysm or aortic valve regurgitation.

Gummas are granulomatous destructive lesions that may involve the skin, bone, or internal organs.

Neurosyphilis

Neurosyphilis can occur during any stage of infection.

Early neurosyphilis commonly manifests as aseptic meningitis or meningovascular disease.

Patients may develop cranial nerve abnormalities, stroke-like syndromes, or spinal cord involvement.

Ocular syphilis can cause uveitis, interstitial keratitis, optic neuritis, retinal disease, or other visual abnormalities.

Otosyphilis can produce sensorineural hearing loss, tinnitus, vertigo, or disequilibrium.

Late neurologic manifestations include general paresis, characterized by progressive cognitive and behavioral deterioration, and tabes dorsalis, characterized by sensory ataxia, lightning-like pains, and impaired proprioception.

The classic Argyll Robertson pupil is small and fails to constrict normally to light but retains accommodation.

Diagnosis

Diagnosis generally requires a combination of clinical assessment and serologic testing.

Direct detection methods include dark-field microscopy, immunofluorescence, and molecular techniques such as PCR, where available.

Dark-field examination can identify T. pallidum from primary or secondary lesions but is generally unsuitable for oral lesions because nonpathogenic oral spirochetes can complicate interpretation.

Serologic testing

Serologic diagnosis usually combines a nontreponemal test with a treponemal test.

Common nontreponemal tests include RPR and VDRL.

Nontreponemal titers correlate approximately with disease activity and are therefore useful for monitoring treatment response.

False-positive nontreponemal tests can occur with pregnancy, autoimmune disease, intravenous drug use, older age, and certain infections.

Treponemal tests include assays such as FTA-ABS, TPPA, TPHA, and treponemal enzyme immunoassays.

Treponemal tests are more specific but usually remain positive for a prolonged period or for life, so their titers are not useful for assessing treatment response.

Many laboratories now use a reverse screening algorithm, beginning with a treponemal immunoassay followed by a quantitative nontreponemal test.

When the treponemal screening assay is reactive but the nontreponemal test is negative, an additional treponemal assay can help clarify whether the result represents previous treated infection, early infection, or a false-positive screening test.

Cerebrospinal fluid evaluation

Lumbar puncture may be indicated when patients have neurologic, ophthalmic, or otologic manifestations suggestive of neurosyphilis, or in selected cases of treatment failure or tertiary disease.

CSF findings may include lymphocytic pleocytosis, increased protein concentration, and a reactive CSF-VDRL.

A reactive CSF-VDRL is highly supportive of neurosyphilis, although a negative result does not completely exclude the diagnosis.

Differential diagnosis

Primary genital lesions may resemble genital herpes, chancroid, lymphogranuloma venereum, granuloma inguinale, traumatic ulcers, malignancy, or fixed drug eruptions.

Secondary syphilis can mimic many conditions, including acute HIV infection, viral exanthems, drug eruptions, erythema multiforme, scabies, fungal disease, and other systemic infections.

Because its clinical manifestations are extremely diverse, syphilis is often described as a “great imitator.”

Treatment of primary, secondary, and early latent syphilis

The traditional first-line treatment is benzathine penicillin G administered intramuscularly.

Patients with early disease generally require a single appropriately dosed injection, provided there is no evidence of neurosyphilis.

Late latent and tertiary syphilis

Late latent syphilis, syphilis of unknown duration, and tertiary syphilis without neurologic involvement generally require multiple weekly doses of benzathine penicillin G.

Neurosyphilis

Neurosyphilis requires high-dose intravenous aqueous crystalline penicillin G for an extended treatment course because adequate concentrations must be achieved in the cerebrospinal fluid.

An alternative regimen involving procaine penicillin plus probenecid may be used in selected circumstances.

Penicillin allergy

For certain nonpregnant patients with early syphilis who cannot receive penicillin, doxycycline may be used as an alternative.

Alternative regimens for late latent disease generally require a longer course than those used for early syphilis.

Macrolide therapy is unreliable because T. pallidum resistance and treatment failures have been documented.

Pregnancy

Penicillin is the only established effective treatment for syphilis during pregnancy and is essential for prevention and treatment of fetal infection.

Pregnant patients who report a penicillin allergy should generally undergo penicillin desensitization so that appropriate penicillin treatment can be administered.

Jarisch–Herxheimer reaction

A Jarisch–Herxheimer reaction may occur within the first 24 hours after starting treatment.

It is characterized by an acute onset of fever, chills, headache, myalgia, and transient worsening of symptoms caused by the inflammatory response to rapid destruction of spirochetes.

It occurs particularly often in early syphilis and should not be mistaken for penicillin allergy.

Follow-up

Sexual partners should be clinically evaluated and tested, and treated when indicated according to the timing and stage of exposure.

Partners with recent exposure to someone diagnosed with primary, secondary, or early latent syphilis may require presumptive treatment even when initial serologic testing is negative.

Treatment response is monitored using quantitative nontreponemal titers, such as RPR or VDRL.

An appropriate decline in nontreponemal titers over time supports successful therapy, whereas persistently high or increasing titers may indicate reinfection, inadequate treatment, or treatment failure.

Patients with late disease require longer-term serologic monitoring than patients with early syphilis.

Patients treated for neurosyphilis may require additional neurologic, ophthalmologic, or audiologic follow-up depending on their presenting manifestations.

Prognosis

Early diagnosis and appropriate treatment generally produce an excellent prognosis and prevent progression to late destructive disease.

Neurologic or cardiovascular damage that has already occurred in advanced syphilis may not completely reverse after antimicrobial treatment.

High-Yield Pattern

Painless indurated genital ulcer → primary syphilis

Diffuse nonpruritic rash involving palms and soles → secondary syphilis

Positive serology without symptoms → latent syphilis

Aortic disease, gummas, or late neurologic manifestations → tertiary syphilis

Neurologic, ocular, or auditory manifestations can occur at any stage → consider neurosyphilis

Diagnosis → treponemal + nontreponemal testing

Treatment → penicillin remains the cornerstone of therapy

Infectious Disease and Microbiology – Surgical site infections

Surgical site infection (SSI), formerly called a surgical wound infection, is an infection occurring at or near an operative site. It may be recognized by purulent drainage, positive cultures from a primarily closed surgical site, reopening of the wound because of infection, or a clinician’s diagnosis of infection.

SSIs are commonly classified as superficial incisional, deep incisional, or organ/space infections, according to the depth and anatomical structures involved.

A superficial incisional SSI involves only the skin and subcutaneous tissue of the incision and typically occurs within the postoperative surveillance period. Findings may include purulent superficial drainage, recovery of microorganisms from an aseptically collected specimen, or characteristic clinical evidence of infection.

A deep incisional SSI involves deeper soft tissues such as fascia and muscle. It may present with deep purulent drainage, abscess formation, wound dehiscence, or radiologic or operative evidence of deep infection.

An organ/space SSI affects an anatomical structure that was entered or manipulated during surgery but lies deeper than the incision. Examples include intra-abdominal abscesses, infected joint spaces, mediastinal infections, and pelvic collections.

Epidemiology

Surgical site infections are among the most important healthcare-associated infections and account for a substantial proportion of infections occurring in surgical patients.

Most SSIs involve the incision itself, while a smaller proportion involve deeper organs or spaces accessed during surgery.

SSIs can substantially prolong hospitalization, increase the likelihood of readmission, and markedly increase healthcare costs.

Many infections become apparent after hospital discharge, making appropriate patient education and postoperative surveillance important.

Risk factors

The risk of infection depends on the number and virulence of contaminating organisms, the patient’s underlying health, and the quality of the surgical technique.

Patient-related risk factors include diabetes, obesity, smoking, malnutrition, extremes of age, immunosuppression, systemic corticosteroid use, prolonged preoperative hospitalization, and active infection at another body site.

Colonization with Staphylococcus aureus, particularly MRSA, can increase the risk of postoperative infection.

Procedure-related factors include a long duration of surgery, foreign material or prosthetic devices, drains, excessive tissue trauma, poor hemostasis, and inappropriate hair removal.

Shaving the operative field substantially before surgery can produce microscopic skin injuries and increase infection risk.

Prevention

Prevention begins with appropriate infection-control practices, surgical asepsis, effective sterilization, operating-room ventilation, careful surgical technique, and appropriate perioperative antimicrobial prophylaxis.

Whenever possible, infections at sites distant from the planned operation should be identified and treated before elective surgery.

Good perioperative blood glucose control is particularly important in patients with diabetes.

Smoking cessation should be encouraged before elective surgery because smoking impairs wound healing and increases postoperative complications.

The preoperative hospital stay should be kept as short as reasonably possible.

Maintaining normal body temperature during and after surgery also helps decrease the risk of SSI.

When antimicrobial prophylaxis is indicated, the drug should be selected according to the type of operation and expected organisms and administered so that effective tissue concentrations are present at the time of incision.

Routine vancomycin prophylaxis is generally inappropriate, but it may be considered in selected patients with a substantial risk of MRSA infection or colonization.

Etiology

Most surgical site pathogens originate from the patient’s own skin, gastrointestinal, or genital flora, depending on the operative site.

The most frequently encountered organisms include Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus species, Enterobacteriaceae, and Enterococcus species.

Operations involving the gastrointestinal or female genital tract may additionally produce infections caused by anaerobic organisms such as Bacteroides species.

Foreign bodies dramatically reduce the bacterial inoculum required to establish infection, which explains the particular concern surrounding prosthetic joints, vascular grafts, cardiac devices, and other implanted materials.

Antimicrobial-resistant organisms, including MRSA, are increasingly important causes of SSI.

Fungal infection, including Candida, may occur in selected high-risk patients.

Unusual organisms or clusters of postoperative infections should raise concern for a common contaminated source or infection-control problem and should be reported to the relevant infection-prevention team.

Clinical presentation

Patients may present with fever, chills, increasing postoperative pain, localized tenderness, or drainage from the operative wound.

Deep incisional or organ/space infection may present primarily with persistent unexplained fever, even when the superficial incision initially appears normal.

Physical examination

The surgical wound should be examined carefully for erythema extending beyond the wound margin, warmth, tenderness, induration, fluctuance, purulent drainage, or separation of the wound edges.

Wound dehiscence can result from infection but may also occur because of mechanical failure or impaired wound healing.

Sternal wounds after cardiac surgery require particular attention because deep infection can lead to mediastinitis or sternal osteomyelitis.

A patient with persistent fever and sternal instability or rocking after cardiac surgery may have a deep infection even when the skin surface appears relatively normal.

Diagnosis

Diagnosis is based on clinical examination together with microbiologic and radiologic evaluation when indicated.

Persistent leukocytosis may support the presence of infection but is nonspecific.

Purulent drainage or aspirated material should be sent for Gram stain and aerobic and anaerobic cultures whenever feasible.

Blood cultures should be obtained when there are signs of systemic infection, bacteremia, sepsis, or deep organ involvement.

Imaging

Imaging is particularly useful when a deep collection or organ/space infection is suspected.

Computed tomography is commonly used to identify postoperative abscesses, fluid collections, fascial involvement, and deeper extension of infection.

Ultrasound may be useful for superficial or intra-abdominal collections and can help guide aspiration or drainage.

A suspected abscess generally requires drainage and microbiologic sampling rather than antimicrobial treatment alone.

Treatment

Management depends on the depth and severity of infection, the operative site, the presence of foreign material, and the patient’s clinical condition.

A superficial incisional infection may sometimes be managed by opening the wound, providing local wound care, and using antibiotics when surrounding cellulitis or systemic manifestations are present.

When antibiotics are required for superficial infections, therapy should primarily cover common skin organisms, especially S. aureus and streptococci.

Deep incisional and organ/space infections usually require broader empiric antimicrobial therapy, followed by narrowing of treatment once culture and susceptibility results are available.

Operations involving the gastrointestinal or female genital tract require coverage of gram-negative enteric organisms and anaerobes in addition to gram-positive bacteria.

Empiric choices in severe infections may include agents such as ampicillin-sulbactam, piperacillin-tazobactam, or an appropriate broad-spectrum cephalosporin or carbapenem, depending on the operative site, patient risk factors, and local antimicrobial-resistance patterns.

MRSA-active treatment should be added when the patient has relevant risk factors or when MRSA is identified.

The duration of antimicrobial therapy depends on source control, infection depth, the responsible organism, presence of prosthetic material, clinical response, and whether drains or residual infected tissue remain.

Surgical management

Source control is essential in many surgical site infections.

An infected wound may need to be opened to permit drainage, debridement, and removal of necrotic tissue.

Deep abscesses generally require percutaneous or operative drainage.

Re-exploration of the surgical site may be necessary when there is persistent infection, inadequate drainage, an anastomotic leak, tissue necrosis, or failure to improve with antimicrobial treatment.

When an implanted prosthetic device becomes infected, definitive management may require removal of the device, depending on the type of implant, organism, duration of infection, and feasibility of salvage.

Wound management

Heavily contaminated surgical wounds may sometimes be left open initially and allowed to heal by secondary intention or undergo delayed primary closure.

Open wounds may require regular irrigation, dressing changes, packing, or negative-pressure wound therapy depending on their size and complexity.

Follow-up

Patients should be instructed to seek medical evaluation if they develop fever, increasing wound pain, spreading redness, swelling, purulent drainage, wound separation, or new systemic symptoms after surgery.

Because many SSIs develop after discharge, postoperative follow-up is important even when the initial hospital course was uncomplicated.

Prognosis

Superficial infections usually have a good outcome when recognized and treated promptly.

Deep and organ/space infections are associated with substantially greater morbidity, prolonged hospitalization, readmission, repeat surgery, and mortality.

Complications

Possible complications include wound dehiscence, deep abscess formation, bacteremia, sepsis, delayed wound healing, and recurrent infection.

Following cardiac surgery, deep infection may result in mediastinitis or sternal osteomyelitis, both of which are serious and potentially life-threatening.

Infection surrounding a prosthetic device can progress to prosthesis infection, frequently requiring prolonged antimicrobial therapy and sometimes removal or replacement of the device.

High-Yield Pattern

Purulent drainage or spreading erythema from a surgical incision → suspect superficial SSI

Deep pain, wound separation, fever, or deep purulent drainage → suspect deep incisional SSI

Persistent postoperative fever with a deep collection on imaging → suspect organ/space SSI

SSI + abscess or necrotic tissue → source control with drainage/debridement is essential

Prosthetic material + persistent infection → consider device-associated infection and possible removal

Infectious Disease and Microbiology – Strongyloidiasis

Strongyloidiasis is an intestinal nematode infection caused mainly by Strongyloides stercoralis. Infection begins when infective larvae in contaminated soil penetrate the skin. Unlike many other intestinal helminths, Strongyloides can complete its life cycle within the human host, allowing autoinfection and persistence of infection for decades.

The disease occurs worldwide but is most common in tropical and subtropical regions, especially in areas with poor sanitation. High prevalence has been reported in parts of South America, Southeast Asia, and other resource-limited regions.

A particularly important feature is that chronic infection may remain asymptomatic for many years after a person leaves an endemic area because continuous autoinfection maintains the parasite within the host.

Major risk factors include residence or travel in endemic areas, walking barefoot or having direct skin contact with contaminated soil, and impaired immunity.

Severe disease is strongly associated with immunosuppression, particularly systemic corticosteroid therapy, solid-organ or hematopoietic stem-cell transplantation, hematologic malignancy, cytotoxic chemotherapy, and TNF-α inhibitors.

Even relatively short courses of corticosteroids can precipitate Strongyloides hyperinfection syndrome in an infected patient.

Coinfection with HTLV-1 is another important risk factor for severe, persistent, and disseminated strongyloidiasis.

Prevention depends primarily on adequate sanitation, avoidance of barefoot exposure to contaminated soil, and recognition of chronic infection before immunosuppressive therapy.

Patients with a history of residence or substantial exposure in endemic areas should be considered for screening before transplantation or major immunosuppressive treatment, particularly before corticosteroid therapy when clinically appropriate.

Life Cycle and Pathophysiology

Adult female worms reside within the mucosa of the duodenum and jejunum.

Eggs produced by the adult worms hatch within the intestine and release rhabditiform larvae.

These larvae may pass in the stool and continue their life cycle in the soil.

Some rhabditiform larvae instead transform into infective filariform larvae while still inside the host.

These infective larvae can penetrate the intestinal mucosa or the perianal skin and re-enter the circulation.

This process is called autoinfection and explains why Strongyloides infection can persist for decades without repeated environmental exposure.

After skin penetration, filariform larvae enter the bloodstream and migrate to the lungs.

They pass through the pulmonary circulation, enter the alveoli, ascend the respiratory tract, are swallowed, and eventually reach the small intestine where they mature into adult worms.

Hyperinfection Syndrome

In immunosuppressed patients, autoinfection can accelerate dramatically.

Large numbers of larvae migrate through the intestine and lungs, producing hyperinfection syndrome.

If larvae spread beyond their usual gastrointestinal and pulmonary life cycle into organs such as the brain, liver, or kidneys, the condition is termed disseminated strongyloidiasis.

Larval migration through the intestinal wall can carry enteric bacteria into the circulation.

This can produce severe gram-negative bacteremia, polymicrobial sepsis, meningitis, or other metastatic bacterial infections.

Clinical Manifestations

Many patients with chronic strongyloidiasis are asymptomatic or have only mild intermittent symptoms.

Skin Manifestations

During acute infection, patients may develop pruritic erythematous papules at the site of larval penetration, commonly on the feet.

A characteristic manifestation of chronic autoinfection is larva currens.

Larva currens consists of a rapidly moving, serpiginous, intensely pruritic urticarial eruption, usually beginning around the perianal region and extending onto the buttocks, thighs, or trunk.

Its rapid migration helps distinguish it from classic cutaneous larva migrans.

Gastrointestinal Disease

Patients may experience intermittent diarrhea, abdominal cramping, diffuse abdominal discomfort, nausea, anorexia, or weight loss.

Rarely, chronic infection can produce malabsorption or nutritional deficiencies.

In severe hyperinfection, gastrointestinal manifestations may include mucosal ulceration, gastrointestinal bleeding, bowel-wall edema, ileus, and intestinal dysfunction.

Pulmonary Disease

Larval migration through the lungs can produce cough, wheezing, bronchospasm, or transient pulmonary infiltrates, resembling a Löffler-type eosinophilic pulmonary syndrome.

In hyperinfection syndrome, pulmonary disease can progress rapidly to diffuse pneumonitis, hypoxemia, respiratory failure, or acute respiratory distress syndrome (ARDS).

Disseminated Disease

Disseminated infection may involve the central nervous system, liver, kidneys, skin, and other organs.

An important diagnostic clue is the development of unexplained gram-negative or polymicrobial sepsis or meningitis, particularly with enteric organisms such as Escherichia coli or Klebsiella, in an immunosuppressed patient with epidemiologic risk for Strongyloides.

Diagnosis

Eosinophilia may occur in chronic uncomplicated infection, but its absence does not exclude strongyloidiasis.

In fact, eosinophilia may disappear in severe hyperinfection, so a normal eosinophil count can be falsely reassuring.

Diagnosis can be established by identifying Strongyloides larvae in stool.

Because larval shedding can be intermittent and low in chronic infection, a single stool examination has limited sensitivity.

Repeated stool examinations improve diagnostic yield.

More sensitive parasitologic methods include stool agar-plate culture, concentration techniques, and molecular detection such as PCR where available.

Serologic testing, commonly by ELISA, is useful for screening and has good sensitivity in immunocompetent patients, although sensitivity may be lower in immunosuppressed individuals.

Duodenal aspirates or biopsy specimens may demonstrate larvae when stool studies are negative but clinical suspicion remains high.

In hyperinfection, larvae may also be found in sputum, bronchoalveolar lavage fluid, or other specimens.

Chest imaging may demonstrate interstitial infiltrates, focal pneumonia-like changes, diffuse pulmonary opacities, or ARDS in severe disease.

Differential Diagnosis

Strongyloidiasis can resemble other helminth infections, including ascariasis, hookworm disease, and cutaneous larva migrans.

Pulmonary manifestations may resemble atypical pneumonia, eosinophilic lung disease, or tropical pulmonary eosinophilia.

Gastrointestinal disease can mimic other causes of chronic diarrhea, malabsorption, or inflammatory bowel disease.

Treatment

Ivermectin is the treatment of choice for uncomplicated strongyloidiasis.

A commonly used regimen is ivermectin 200 μg/kg orally once daily for 1–2 days, although treatment schedules may vary depending on the clinical situation.

Albendazole is less effective and is generally considered an alternative when ivermectin cannot be used.

Hyperinfection and Disseminated Strongyloidiasis

Hyperinfection syndrome is a medical emergency.

Treatment requires daily ivermectin, generally continued until clinical improvement occurs and parasitologic examinations remain negative for an adequate period.

Patients with ileus or severe gastrointestinal dysfunction may have poor absorption of oral ivermectin.

In exceptional life-threatening situations where oral or enteral therapy cannot be reliably absorbed, alternative routes of ivermectin administration have been used under specialist supervision and regulatory or compassionate-use arrangements.

Associated bacterial sepsis must be treated aggressively with appropriate antibacterial therapy and supportive care.

Whenever possible, immunosuppressive therapy should be reduced, especially corticosteroids.

Follow-Up

After treatment of uncomplicated infection, repeat stool testing may be performed to document parasitologic clearance, particularly when symptoms persist or the patient is immunocompromised.

Serologic antibody levels generally decline over months after successful treatment and can sometimes assist with follow-up.

In disseminated or hyperinfection disease, stool and other relevant specimens should be examined repeatedly during treatment until evidence of active infection has resolved.

Prognosis

Uncomplicated strongyloidiasis usually responds well to appropriate therapy.

By contrast, hyperinfection and disseminated strongyloidiasis are potentially fatal, particularly in patients receiving corticosteroids or other major immunosuppressive therapies.

Complications

The most serious complications include hyperinfection syndrome, disseminated larval infection, severe pneumonitis, ARDS, gram-negative bacteremia, polymicrobial sepsis, meningitis, gastrointestinal bleeding, and multiorgan failure.

High-Yield Pattern

Endemic soil exposure + chronic intermittent GI symptoms ± eosinophilia + rapidly migrating perianal rash (larva currens) → consider strongyloidiasis.

Steroids or major immunosuppression + unexplained pulmonary deterioration + gram-negative sepsis → urgently consider Strongyloides hyperinfection.

Diagnosis → repeated stool examination / agar culture / PCR / serology.

Treatment → ivermectin.

Hyperinfection → daily ivermectin + reduce immunosuppression + treat associated sepsis.

Infectious Disease and Microbiology – Stomatitis

Stomatitis is inflammation of the oral mucosa, which may be localized or widespread. It can result from infectious causes, trauma, allergy, nutritional deficiencies, medications, smoking, or systemic disease.

⸻

Common forms include recurrent aphthous stomatitis, herpetic stomatitis, hand-foot-and-mouth disease, herpangina, oral candidiasis, acute necrotizing ulcerative gingivitis, and noma.

⸻

Recurrent aphthous stomatitis, herpetic stomatitis, and hand-foot-and-mouth disease are common. Oral candidiasis is particularly frequent in immunocompromised patients, people receiving broad-spectrum antibiotics, diabetics, and patients treated with systemic or inhaled corticosteroids.

⸻

Herpangina, hand-foot-and-mouth disease, and primary herpetic gingivostomatitis occur predominantly in children, whereas acute necrotizing ulcerative gingivitis is seen more often in adolescents and young adults.

⸻

Noma, also called cancrum oris or gangrenous stomatitis, is a severe destructive disease involving oral soft tissue and bone. It occurs mainly in severely malnourished children, particularly in resource-limited settings.

⸻

Important risk factors for stomatitis include smoking, alcohol use, antibiotic therapy, corticosteroid or other immunosuppressive treatment, HIV infection, malignancy, poor oral hygiene, and problematic dentures.

⸻

General prevention includes smoking cessation, adequate oral hygiene, careful denture cleaning, and removal of complete dentures during sleep.

⸻

Etiology

Oral candidiasis is caused by Candida species and commonly affects the tongue, buccal mucosa, palate, and gingiva.

⸻

The exact cause of recurrent aphthous stomatitis is unknown. It is generally regarded as an inflammatory condition rather than a direct infection.

⸻

Viruses are common causes of infectious stomatitis. Herpes simplex virus can cause primary and recurrent herpetic stomatitis, while enteroviruses such as coxsackieviruses cause herpangina and hand-foot-and-mouth disease.

⸻

Acute necrotizing ulcerative gingivitis, historically called Vincent stomatitis or trench mouth, is associated with a polymicrobial anaerobic flora including Prevotella intermedia, Fusobacterium species, and oral spirochetes.

⸻

Noma is also polymicrobial and is associated with anaerobic and fusospirochetal organisms such as Fusobacterium nucleatum and other oral bacteria.

⸻

Noninfectious causes include drug or food allergy, contact reactions, vitamin deficiencies, trauma from dentures, smoking, anemia, uremia, Behçet disease, collagen vascular disorders, and other systemic illnesses.

⸻

Riboflavin deficiency may cause angular stomatitis, while niacin deficiency can produce oral abnormalities as part of pellagra.

⸻

Clinical Presentation

Symptoms depend on the underlying cause. Patients may complain of oral pain, gingival tenderness, difficulty eating, fever, or malaise.

⸻

Oral Candidiasis

Pseudomembranous oral candidiasis produces creamy-white, curd-like plaques that can usually be wiped away, leaving an erythematous underlying surface.

⸻

Erythematous candidiasis produces red, friable, tender plaques rather than the classic white coating.

⸻

Aphthous Stomatitis

Recurrent aphthous stomatitis presents as small, round or oval, clearly demarcated painful ulcers within the oral cavity.

⸻

These lesions usually heal spontaneously and typically do not leave scars.

⸻

Herpetic Stomatitis

Primary herpetic gingivostomatitis occurs mainly in children and often begins with fever, malaise, and fatigue, followed by multiple painful vesicles.

⸻

The vesicles rupture and become moist ulcers surrounded by an erythematous inflammatory border.

⸻

Recurrent herpes can be precipitated by sun exposure, emotional stress, trauma, fever, or other systemic illness.

⸻

Herpetic gingivostomatitis generally favors the anterior oral cavity, including the gingiva, lips, tongue, and hard palate.

⸻

Herpangina

Herpangina usually begins with fever, sore throat, and painful swallowing.

⸻

Small vesicles and ulcers surrounded by erythematous rings occur mainly on the soft palate, uvula, tonsillar pillars, and posterior pharyngeal wall.

⸻

This posterior location helps distinguish herpangina from herpetic gingivostomatitis.

⸻

Hand-Foot-and-Mouth Disease

Hand-foot-and-mouth disease generally causes oral ulcers accompanied by skin lesions on the hands and feet.

⸻

Lesions can also appear on the buttocks and groin. The illness is usually mild and self-limited.

⸻

Acute Necrotizing Ulcerative Gingivitis

Necrotizing ulcerative gingivitis produces painful gingival necrosis, especially involving the interdental papillae.

⸻

The gingiva develops a characteristic punched-out, eroded appearance, often covered by a gray pseudomembrane.

⸻

Halitosis and gingival bleeding are common.

⸻

Noma

Noma is substantially more aggressive than ordinary necrotizing gingivitis.

⸻

It can rapidly progress from oral ulceration to extensive destruction of the cheek, lips, gingiva, jaw, and facial soft tissues.

⸻

Diagnosis

Diagnosis is primarily based on the clinical appearance and distribution of the oral lesions.

⸻

Cultures, stains, and molecular tests may be useful when the diagnosis is uncertain or the patient is immunocompromised.

⸻

In oral candidiasis, microscopy may demonstrate budding yeast with or without pseudohyphae.

⸻

For suspected herpes infection, PCR is generally the most useful confirmatory test. Viral culture or direct antigen testing may also be performed.

⸻

Historically, a Tzanck smear may demonstrate multinucleated giant cells, although it is neither highly specific nor the preferred modern diagnostic method.

⸻

Any persistent, chronically recurrent, atypical, indurated, or nonhealing oral lesion should be biopsied to exclude malignancy or another serious disorder.

⸻

Differential Diagnosis

The principal differential diagnoses include herpetic stomatitis, herpangina, hand-foot-and-mouth disease, recurrent aphthous stomatitis, oral candidiasis, necrotizing ulcerative gingivitis, and noma.

⸻

Treatment

Most forms require supportive and cause-specific treatment.

⸻

Oral Candidiasis

Mild oral candidiasis may be treated with topical agents such as nystatin or clotrimazole.

⸻

Moderate-to-severe disease is commonly treated with oral fluconazole.

⸻

Predisposing factors such as unnecessary antibiotics, poorly controlled diabetes, improper denture hygiene, or corticosteroid exposure should be corrected when possible.

⸻

Aphthous Stomatitis

Treatment is mainly symptomatic.

⸻

Topical anesthetics, antiseptic mouth rinses, and topical corticosteroids may reduce pain and inflammation.

⸻

Systemic therapy is reserved for severe or refractory disease and should generally be directed by a clinician experienced in recurrent oral ulceration.

⸻

Herpetic Stomatitis

Significant primary herpetic stomatitis may be treated with acyclovir or valacyclovir, particularly when therapy is started early.

⸻

Severely immunocompromised patients may require intravenous acyclovir.

⸻

Acyclovir-resistant HSV infection may require foscarnet, particularly in advanced immunosuppression.

⸻

Coxsackievirus Disease

Herpangina and hand-foot-and-mouth disease usually require no specific antiviral treatment.

⸻

Management consists of hydration, analgesia, and supportive care.

⸻

Necrotizing Ulcerative Gingivitis

Treatment includes professional oral cleaning or debridement, meticulous oral hygiene, pain control, and antibiotics when systemic or extensive disease is present.

⸻

Metronidazole or penicillin-class antibiotics may be used according to the clinical situation.

⸻

Noma

Noma requires urgent and comprehensive management, including antibiotic therapy, nutritional rehabilitation, wound care, treatment of dehydration or systemic illness, and removal of loose teeth or necrotic tissue when indicated.

⸻

Major facial deformities may later require reconstructive surgery.

⸻

Additional Care

Smoking should be discontinued, problematic dentures should be corrected, and oral hygiene should be optimized.

⸻

Topical anesthetics and systemic analgesics can help control oral pain.

⸻

Patients who cannot maintain adequate oral intake because of severe pain may require liquid nutrition, oral rehydration, intravenous fluids, or hospitalization.

⸻

Spicy, acidic, or otherwise irritating foods may worsen symptoms and can be temporarily avoided.

⸻

Follow-Up

Most viral stomatitis and uncomplicated aphthous episodes resolve within approximately 7–14 days.

⸻

Persistent, recurrent, unusual, or nonhealing lesions require reassessment and often biopsy.

⸻

Complications

Severe herpes infection can occasionally involve the eye or central nervous system, particularly in immunocompromised patients.

⸻

Severe stomatitis can cause dehydration, malnutrition, and inability to maintain oral intake.

⸻

Noma can result in severe facial destruction, functional disability, sepsis, and death.

⸻

High-Yield Pattern

White removable plaques → oral candidiasis

⸻

Small recurrent painful ulcers → aphthous stomatitis

⸻

Anterior oral vesicles/ulcers + gingivitis → herpetic gingivostomatitis

⸻

Posterior oral vesicles/ulcers → herpangina

⸻

Oral ulcers + hand and foot lesions → hand-foot-and-mouth disease

⸻

Painful punched-out necrotic gingiva + halitosis → acute necrotizing ulcerative gingivitis

⸻

Rapidly destructive oral/facial necrosis in a malnourished child → noma