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.

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

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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.

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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.

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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.

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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.

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

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Etiology

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

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

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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.

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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.

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

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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.

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

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Clinical Presentation

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

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Oral Candidiasis

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

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

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Aphthous Stomatitis

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

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

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Herpetic Stomatitis

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

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

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

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

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Herpangina

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

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

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This posterior location helps distinguish herpangina from herpetic gingivostomatitis.

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Hand-Foot-and-Mouth Disease

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

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

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Acute Necrotizing Ulcerative Gingivitis

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

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

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Halitosis and gingival bleeding are common.

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Noma

Noma is substantially more aggressive than ordinary necrotizing gingivitis.

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

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Diagnosis

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

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

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

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

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

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

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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.

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Treatment

Most forms require supportive and cause-specific treatment.

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Oral Candidiasis

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

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

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

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Aphthous Stomatitis

Treatment is mainly symptomatic.

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

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

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Herpetic Stomatitis

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

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Severely immunocompromised patients may require intravenous acyclovir.

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

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Coxsackievirus Disease

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

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Management consists of hydration, analgesia, and supportive care.

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Necrotizing Ulcerative Gingivitis

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

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

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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.

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Major facial deformities may later require reconstructive surgery.

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Additional Care

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

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Topical anesthetics and systemic analgesics can help control oral pain.

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

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

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Follow-Up

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

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

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Complications

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

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

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

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High-Yield Pattern

White removable plaques → oral candidiasis

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Small recurrent painful ulcers → aphthous stomatitis

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Anterior oral vesicles/ulcers + gingivitis → herpetic gingivostomatitis

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Posterior oral vesicles/ulcers → herpangina

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

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

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

Infectious Disease and Microbiology – Sporotrichosis

Sporotrichosis is a dimorphic fungal infection caused by Sporothrix schenckii complex organisms. It most often develops after traumatic inoculation of the fungus into the skin and classically appears as lymphocutaneous disease, although fixed cutaneous, disseminated cutaneous, pulmonary, osteoarticular, and systemic forms can also occur.

The infection is particularly associated with tropical and subtropical regions of the Americas, although sporotrichosis occurs worldwide. Environmental exposure to contaminated soil, plants, rose bushes, sphagnum moss, hay, timber, and other vegetation can lead to inoculation through minor skin injuries.

Zoonotic transmission is also recognized. Infection has been associated with several animals, but cats are an especially important source of human sporotrichosis, particularly when infected animals have ulcerated skin lesions containing large numbers of organisms.

People with frequent outdoor or occupational exposure are at greater risk, including farmers, gardeners, florists, horticultural workers, forestry workers, miners, and veterinarians.

Disseminated or extracutaneous disease is uncommon and occurs mainly in people with impaired host defenses. Important predisposing conditions include advanced HIV infection, chronic corticosteroid therapy, chemotherapy, alcoholism, diabetes mellitus, and chronic pulmonary disease.

Sporothrix is a thermally dimorphic fungus. In the environment and at room temperature, it grows as a mold with branching hyphae, while in human tissue it is found primarily in a yeast form.

The yeast forms are generally small and may appear elongated or cigar-shaped. Because the fungal burden in tissue can be low, organisms are often difficult to identify directly on routine microscopy.

The incubation period after inoculation is usually approximately 1–12 weeks.

The first lesion generally appears as a small painless papule at the site of inoculation. It may gradually enlarge, become reddish or violaceous, develop into a pustule or nodule, and eventually ulcerate with a small amount of serous or serosanguineous drainage.

The lesion is usually not very tender. Significant pain can suggest secondary bacterial infection or an alternative diagnosis.

In lymphocutaneous sporotrichosis, secondary nodules develop progressively along the lymphatic vessels draining the original lesion. This produces the classic ascending chain of subcutaneous nodules.

This characteristic pattern is often described as sporotrichoid lymphatic spread.

A useful clinical sequence is:

Skin trauma involving vegetation or an infected cat → painless papule → ulceration → additional nodules ascending along lymphatic channels.

In fixed cutaneous sporotrichosis, the infection remains localized to the original inoculation site without lymphatic spread. The lesion can persist for prolonged periods if untreated.

Disseminated cutaneous sporotrichosis produces multiple papules, nodules, or ulcers at noncontiguous sites. This presentation should raise concern for an underlying immunocompromising condition and possible systemic dissemination.

Osteoarticular disease may involve joints, bones, or both. Patients can develop a slowly progressive chronic monoarthritis or oligoarthritis, with swelling, pain during movement, and progressive loss of function.

Long-standing osteoarticular disease may produce osteomyelitis, joint destruction, or draining sinus tracts.

Pulmonary sporotrichosis usually results from inhalation of fungal conidia rather than direct skin inoculation. It is uncommon and tends to occur in patients with underlying chronic lung disease or heavy alcohol use.

Pulmonary disease can resemble tuberculosis, with chronic cough, constitutional symptoms, upper-lobe abnormalities, cavitary lesions, and progressive pulmonary destruction.

Severely immunocompromised patients may develop disseminated sporotrichosis, with involvement of skin, joints, bones, lungs, and occasionally the central nervous system.

Sporothrix meningitis is rare but can occur, particularly in patients with significant immunosuppression. It usually requires prolonged antifungal therapy.

Diagnosis

The most reliable diagnostic method is fungal culture of material obtained from an affected site.

Appropriate specimens may include skin biopsy tissue, lesion drainage, synovial fluid, bone specimens, respiratory secretions, or cerebrospinal fluid, depending on the clinical presentation.

Culture should include fungal media such as Sabouraud dextrose agar. Growth of the mold form followed by appropriate identification establishes the diagnosis.

Histopathology can demonstrate granulomatous and suppurative inflammation, but fungal organisms are often sparse.

Special stains such as periodic acid–Schiff (PAS) and Gomori methenamine silver (GMS) can improve visualization of fungal elements.

The organisms in tissue may appear as small oval or cigar-shaped yeasts, usually measuring only a few micrometers.

An asteroid body, consisting of a yeast surrounded by eosinophilic material, can occasionally be seen histologically. It is suggestive but not diagnostic of sporotrichosis.

Because of the low organism burden, multiple biopsies or cultures may occasionally be required before the infection is confirmed.

There is no routinely accepted serologic test that reliably establishes the diagnosis in typical cutaneous disease.

Differential Diagnosis

The differential diagnosis of lymphocutaneous sporotrichosis includes other infections producing nodules along lymphatic channels, especially:

Mycobacterium marinum

Nontuberculous mycobacteria

Nocardia species

Cutaneous leishmaniasis

Tularemia

and selected bacterial skin infections.

Pulmonary sporotrichosis may resemble tuberculosis, nontuberculous mycobacterial infection, histoplasmosis, coccidioidomycosis, chronic bacterial lung infection, sarcoidosis, or malignancy.

Treatment

Itraconazole is the preferred first-line therapy for uncomplicated lymphocutaneous and fixed cutaneous sporotrichosis.

Treatment generally continues for several months and should usually extend beyond complete clinical resolution of lesions to reduce the risk of relapse.

Because itraconazole absorption can vary considerably, therapeutic drug monitoring may be useful in prolonged, severe, or treatment-refractory infection.

Terbinafine can be considered as an alternative for uncomplicated cutaneous disease when itraconazole cannot be used.

Historically, saturated solution of potassium iodide (SSKI) was widely used and can still be effective for cutaneous sporotrichosis.

Potassium iodide therapy is usually started at a low dose and gradually increased. Important adverse effects include nausea, rash, salivary-gland enlargement, excessive lacrimation, and symptoms of iodism.

Fluconazole is generally less effective than itraconazole, while voriconazole has poor activity against Sporothrix and is not considered a preferred treatment.

Local heat therapy has occasionally been used for limited cutaneous disease because Sporothrix grows poorly at higher temperatures, although systemic antifungal therapy remains preferable for established infection.

Osteoarticular sporotrichosis requires prolonged antifungal therapy, commonly with itraconazole for many months and sometimes approaching one year.

Patients with extensive joint destruction or osteomyelitis may require orthopedic consultation and surgical management.

Severe pulmonary, disseminated, or life-threatening sporotrichosis is generally treated initially with intravenous liposomal amphotericin B.

Once substantial clinical improvement occurs, therapy can usually be changed to itraconazole for prolonged consolidation treatment.

Central nervous system disease also generally requires initial treatment with amphotericin B followed by prolonged azole therapy.

Whenever possible, underlying immunosuppression should be reduced or corrected.

Prevention

Prevention focuses on reducing traumatic inoculation. Protective gloves, long sleeves, and appropriate footwear should be used when handling soil, plants, wood, hay, or other potentially contaminated material.

Skin injuries sustained during outdoor work should be cleaned promptly.

People handling cats with suspected sporotrichosis should use gloves and protective clothing, particularly when touching ulcerated lesions or contaminated secretions.

Prognosis

Localized cutaneous and lymphocutaneous sporotrichosis generally have an excellent prognosis when appropriately treated.

The outlook is less favorable in pulmonary, disseminated, osteoarticular, and CNS disease, particularly in patients with severe immunosuppression.

Important complications include chronic arthritis, osteomyelitis, progressive pulmonary disease, disseminated infection, and meningitis.

High-Yield Summary

Rose thorn / gardening / soil / infected cat exposure → painless skin papule → ulceration → ascending lymphatic nodules = sporotrichosis.

Diagnosis → fungal culture, often supported by biopsy with PAS or GMS staining.

Localized cutaneous disease → itraconazole.

Severe disseminated or CNS disease → amphotericin B initially, followed by prolonged itraconazole.

Infectious Disease and Microbiology – Sinusitis

Sinusitis, more accurately termed rhinosinusitis, is symptomatic inflammation of the mucosa of the nasal cavity and paranasal sinuses. The major paranasal sinuses are the maxillary, ethmoid, frontal, and sphenoid sinuses.

Classification by Duration

Acute rhinosinusitis: symptoms lasting <4 weeks.

Subacute rhinosinusitis: symptoms lasting approximately 4–12 weeks.

Chronic rhinosinusitis (CRS): symptoms persisting for ≥12 weeks.

Recurrent acute rhinosinusitis: ≥4 distinct episodes per year, with resolution of symptoms between episodes.

Acute exacerbation of chronic rhinosinusitis: worsening or development of new symptoms in a patient with underlying chronic disease.

Acute rhinosinusitis is overwhelmingly viral. Only a small proportion of viral upper respiratory infections develop secondary acute bacterial rhinosinusitis (ABRS).

The most important bacterial causes of community-acquired acute bacterial rhinosinusitis are:

1. Streptococcus pneumoniae

2. Nontypeable Haemophilus influenzae

3. Moraxella catarrhalis — particularly important in children.

Other organisms, including Staphylococcus aureus, streptococci, anaerobes, and gram-negative bacilli, become more relevant in particular clinical settings.

Odontogenic sinusitis is commonly polymicrobial and may contain oral anaerobic organisms in addition to aerobic bacteria. It particularly involves the maxillary sinus because of its anatomical relationship to the upper teeth.

Important risk factors include allergic rhinitis, smoking and environmental irritants, nasal polyps, deviated nasal septum, tumors, foreign bodies, impaired mucociliary clearance, cystic fibrosis, immunodeficiency, and dental infection.

The pathogenesis frequently begins with a viral upper respiratory infection.

Viral inflammation produces mucosal edema → obstruction of sinus ostia → impaired sinus drainage → retention of secretions → impaired mucociliary clearance.

These conditions may subsequently permit secondary bacterial infection.

A key clinical challenge is distinguishing viral rhinosinusitis from acute bacterial rhinosinusitis because purulent nasal secretions alone do not reliably indicate bacterial infection.

When to Suspect Acute Bacterial Rhinosinusitis

Three clinical patterns are particularly useful.

Persistent illness: nasal discharge or daytime cough/facial pressure persists for approximately 10 days or longer without improvement.

Severe onset: prominent fever with purulent nasal discharge or significant facial pain persisting for several consecutive days at the beginning of illness.

“Double worsening”: the patient initially improves from a viral upper respiratory infection and then develops new or worsening fever, nasal discharge, facial pain, or cough.

This is sometimes called double sickening.

Typical symptoms include nasal obstruction/congestion, anterior or posterior nasal discharge, facial pressure or pain, reduced sense of smell, headache, cough, halitosis, and occasionally fever.

Maxillary tooth pain, particularly when unilateral, may support maxillary sinus involvement. Dental pathology should also raise suspicion for an odontogenic source.

Pain or pressure may occur over the affected sinus and sometimes becomes more noticeable when bending forward, although this finding is not sufficiently specific to establish the diagnosis.

Chronic rhinosinusitis typically presents with prolonged nasal obstruction, nasal drainage, facial pressure, and/or reduced smell, with objective evidence of sinonasal inflammation required to support the diagnosis.

Chronic rhinosinusitis is commonly divided into:

CRS with nasal polyps (CRSwNP)

and

CRS without nasal polyps (CRSsNP).

Chronic rhinosinusitis with nasal polyps is strongly associated with type 2 airway inflammation, and frequently coexists with asthma.

The combination of asthma + chronic rhinosinusitis with nasal polyps + respiratory reactions to aspirin/other COX-1–inhibiting NSAIDs suggests aspirin-exacerbated respiratory disease (AERD).

Diagnosis

Most uncomplicated cases of acute rhinosinusitis are diagnosed clinically.

Routine laboratory testing is usually unnecessary.

Plain sinus radiographs are generally not recommended for routine diagnosis because imaging abnormalities cannot reliably distinguish viral from bacterial rhinosinusitis.

Similarly, CT should not routinely be performed for uncomplicated acute bacterial rhinosinusitis.

A CT scan of the paranasal sinuses becomes important when complications are suspected, symptoms are recurrent or chronic, the diagnosis is uncertain, or surgical planning is required.

CT findings can include mucosal thickening, sinus opacification, air-fluid levels, polyps, and obstruction of sinus drainage pathways.

MRI is particularly useful when there is concern for orbital, intracranial, soft-tissue, vascular, or invasive fungal complications.

Routine cultures of ordinary nasal secretions are poor predictors of organisms within the affected sinus and generally should not guide antibiotic therapy.

When microbiologic diagnosis is necessary because of severe disease, treatment failure, immunocompromise, unusual organisms, or complications, specimens obtained by sinus aspiration or endoscopically directed middle-meatal sampling are substantially more useful.

Treatment of Acute Viral Rhinosinusitis

Most cases require supportive treatment rather than antibiotics.

Useful measures can include analgesics, saline nasal irrigation, and intranasal corticosteroids, particularly when concomitant allergic rhinitis is present.

Topical nasal decongestants such as oxymetazoline can provide temporary symptomatic relief but should generally be limited to a short course because prolonged use can produce rhinitis medicamentosa (rebound congestion).

Antihistamines are most useful when an allergic component is present. They are not routinely necessary simply because a patient has acute infectious sinusitis.

Treatment of Acute Bacterial Rhinosinusitis

When antibiotics are indicated, amoxicillin-clavulanate is commonly preferred as initial empiric therapy.

Antibiotic selection should consider age, severity, allergy history, recent antimicrobial exposure, local resistance patterns, comorbidities, and risk for resistant organisms.

A major change from older recommendations is that macrolides such as azithromycin and clarithromycin and trimethoprim-sulfamethoxazole are generally not preferred for empiric ABRS because of substantial antimicrobial resistance among common respiratory pathogens.

Respiratory fluoroquinolones such as levofloxacin or moxifloxacin have activity against common pathogens but are generally reserved for selected situations, including certain patients with significant beta-lactam allergy, because of their adverse-effect profile and antimicrobial-stewardship considerations.

For uncomplicated ABRS in adults, contemporary practice generally favors a shorter antibiotic course when the patient responds appropriately rather than the routinely prolonged 10–14-day courses used historically.

Chronic Rhinosinusitis

The management of chronic rhinosinusitis differs substantially from acute bacterial sinusitis because CRS is primarily a chronic inflammatory disorder, not simply a persistent bacterial infection.

Core medical therapy includes saline nasal irrigation and intranasal corticosteroids.

Antibiotics are not routinely required for every patient with chronic rhinosinusitis and are used selectively according to the clinical circumstances.

Short courses of systemic corticosteroids may be considered in selected patients, particularly those with severe nasal polyposis, but their risks must be considered.

Patients with persistent disease despite appropriate medical treatment may require ENT evaluation and functional endoscopic sinus surgery (FESS).

Invasive Fungal Rhinosinusitis

Acute invasive fungal rhinosinusitis is a medical and surgical emergency.

It occurs predominantly in patients with profound immunocompromise, uncontrolled diabetes—especially diabetic ketoacidosis—or other major predisposing conditions.

Important pathogens include fungi of the order Mucorales (Rhizopus, Mucor, and related organisms) and Aspergillus species.

Warning manifestations include severe facial pain, facial swelling, fever, ophthalmoplegia, visual abnormalities, cranial nerve abnormalities, and necrotic tissue of the nasal cavity or palate.

A black necrotic eschar in an appropriate high-risk patient is particularly concerning, although its absence does not exclude invasive fungal disease.

Suspected invasive fungal rhinosinusitis requires urgent ENT evaluation, nasal endoscopy, tissue biopsy for histopathology and culture, appropriate imaging, systemic antifungal therapy, and aggressive surgical debridement of necrotic tissue.

For mucormycosis, a lipid formulation of amphotericin B is a major initial treatment option. For invasive aspergillosis, voriconazole is an important first-line antifungal agent.

Complications

Although uncommon, complications of bacterial sinusitis can be life-threatening because of the close anatomical relationship of the sinuses to the orbit, brain, meninges, and intracranial venous system.

Orbital complications are particularly associated with ethmoid sinusitis and include preseptal cellulitis, orbital cellulitis, subperiosteal abscess, and orbital abscess.

Important warning signs are periorbital swelling, proptosis, ophthalmoplegia, pain with eye movement, diplopia, or decreased visual acuity.

These findings warrant urgent evaluation.

Frontal sinusitis can rarely produce osteomyelitis of the frontal bone with a subperiosteal abscess, producing the characteristic forehead swelling known as Pott puffy tumor.

Intracranial complications include meningitis, brain abscess, epidural abscess, subdural empyema, and septic cavernous sinus thrombosis.

A patient with sinusitis who develops severe or progressive headache, altered mental status, meningismus, focal neurologic deficits, seizures, orbital abnormalities, or significant facial swelling requires urgent evaluation for complications.

High-Yield Clinical Pattern

Viral URI → mucosal edema → sinus ostial obstruction → impaired drainage → secondary bacterial infection in a minority of patients.

Symptoms <10 days and improving → usually viral → supportive treatment.

≥10 days without improvement → consider acute bacterial rhinosinusitis.

Severe onset → consider acute bacterial rhinosinusitis.

Initial improvement followed by worsening (“double worsening”) → consider acute bacterial rhinosinusitis.

Most important ABRS organisms:

S. pneumoniae + H. influenzae + M. catarrhalis (especially children).

Typical empiric first-line antibiotic when indicated:

Amoxicillin-clavulanate.

Orbital signs, neurologic abnormalities, severe headache, or immunocompromised patient with necrotic nasal tissue → investigate urgently for a complicated or invasive infection.

Infectious Disease and Microbiology – Shigellosis

Shigellosis is an acute bacterial intestinal infection caused by Shigella species. Clinical disease ranges from mild watery diarrhea to severe inflammatory dysentery characterized by bloody, mucoid stools, abdominal cramps, fever, and tenesmus.

Shigella organisms are small, gram-negative, nonmotile, non-spore-forming facultative anaerobic bacilli belonging to the Enterobacterales. They are highly adapted to humans, who constitute the major reservoir.

The four major species are Shigella sonnei, S. flexneri, S. dysenteriae, and S. boydii.

S. sonnei predominates in many higher-income countries, whereas S. flexneri remains an important cause in lower-resource settings. S. dysenteriae type 1 is particularly important because it produces Shiga toxin and has historically caused severe epidemic dysentery.

Transmission occurs predominantly by the fecal–oral route, either directly from person to person or indirectly through contaminated food, water, hands, or fomites.

An important microbiologic characteristic of Shigella is its extremely low infectious dose. Ingestion of only a small number of organisms can produce disease. Consequently, person-to-person transmission can occur readily.

Important risk groups include young children, childcare attendees and workers, household contacts, travelers to areas with inadequate sanitation, people experiencing homelessness, residents of crowded institutions, and men who have sex with men (MSM).

Outbreaks are particularly associated with crowding, inadequate sanitation, poor access to clean water, childcare settings, institutions, and settings involving close person-to-person contact.

After ingestion, Shigella survives passage through the stomach and reaches the intestine. The organisms primarily infect the colon, invading the intestinal epithelium and producing an intense inflammatory response.

Shigella penetrates the colonic mucosa, multiplies intracellularly, and spreads from cell to cell. The resulting epithelial destruction, ulceration, and intense neutrophilic inflammation account for the characteristic blood, mucus, and leukocytes in the stool.

S. dysenteriae type 1 produces Shiga toxin, which inhibits protein synthesis by targeting the 60S ribosomal subunit. Systemic effects of the toxin can contribute to hemolytic uremic syndrome (HUS).

The incubation period is usually approximately 1–3 days, although it can vary depending on the infecting strain and inoculum.

Illness frequently begins with fever, malaise, anorexia, abdominal cramps, and watery diarrhea. In more severe disease, the diarrhea subsequently becomes inflammatory and bloody.

The classic manifestation is bacillary dysentery: frequent passage of small-volume stools containing blood and mucus, accompanied by severe abdominal cramping and tenesmus.

Tenesmus is the painful and persistent sensation of needing to defecate despite an empty or nearly empty rectum. It reflects intense inflammation of the distal colon and rectum.

Physical examination may demonstrate fever, abdominal tenderness, hyperactive bowel sounds, and signs of dehydration. Severe disease may produce systemic toxicity.

Young children are particularly vulnerable to dehydration, electrolyte abnormalities, hypoglycemia, and neurologic complications.

Most uncomplicated cases are self-limited, but severe shigellosis can produce substantial fluid and electrolyte losses. Assessment of hydration status is therefore one of the most important components of initial evaluation.

When diagnostic testing is indicated, modern stool molecular testing or stool culture can identify Shigella. Culture remains particularly useful because an isolate can undergo antimicrobial susceptibility testing, which has become increasingly important because antimicrobial resistance is common.

Patients with bloody diarrhea, severe illness, fever with inflammatory diarrhea, immunocompromise, outbreak-associated disease, or significant epidemiologic/public-health implications are particularly likely to benefit from stool testing.

Fecal leukocytes or inflammatory markers can support the presence of inflammatory diarrhea but are not specific for shigellosis and generally do not establish the diagnosis.

Blood cultures are not routinely positive in uncomplicated disease. They may be appropriate in patients with severe systemic illness, suspected bacteremia, or significant immunocompromise.

Laboratory evaluation in severe cases may demonstrate metabolic acidosis, electrolyte abnormalities, renal dysfunction, or hypoglycemia. When HUS is suspected, the CBC, platelet count, peripheral blood smear, creatinine, and markers of hemolysis become particularly important.

Imaging is not routinely required for uncomplicated shigellosis. Abdominal imaging is reserved primarily for suspected complications such as toxic megacolon, intestinal obstruction, perforation, or another acute abdominal process.

The differential diagnosis of bloody inflammatory diarrhea includes Campylobacter, Salmonella, Shiga toxin-producing Escherichia coli (STEC), Yersinia enterocolitica, Clostridioides difficile, and Entamoeba histolytica, among other infectious and noninfectious causes.

Distinguishing Shigella from STEC can be especially important because antibiotic treatment is generally avoided in suspected STEC infection due to concern for an increased risk of HUS.

The foundation of treatment is fluid and electrolyte replacement. Oral rehydration is preferred whenever the patient can drink adequately, whereas severe dehydration or inability to tolerate oral fluids may require intravenous isotonic fluids.

Antibiotics are not automatically required for every mild case of shigellosis. They are particularly considered for severe disease, dysentery, immunocompromised patients, patients at increased risk of complications, and circumstances in which shortening fecal shedding may have important public-health benefits.

When antimicrobial therapy is indicated, treatment should increasingly be guided by local resistance patterns and, whenever possible, antimicrobial susceptibility testing.

Depending on susceptibility and clinical circumstances, treatment options can include azithromycin, ciprofloxacin, or ceftriaxone. However, resistance to several traditional agents has become increasingly important, and empiric choices should therefore reflect current local and public-health recommendations.

Multidrug-resistant and extensively drug-resistant (XDR) Shigella have emerged in multiple regions. Resistance can involve ampicillin, trimethoprim-sulfamethoxazole, fluoroquinolones, azithromycin, and third-generation cephalosporins, making microbiologic diagnosis and susceptibility testing particularly valuable in severe or persistent disease.

Antimotility medications such as loperamide and diphenoxylate should generally be avoided in bloody or severe inflammatory diarrhea, because slowing intestinal transit can potentially worsen invasive disease or delay pathogen clearance.

Children with diarrhea should continue appropriate feeding and nutritional support rather than undergoing unnecessary dietary restriction. In settings where recommended for childhood acute diarrhea, zinc supplementation can reduce the duration and severity of diarrheal illness.

Hospitalization may be necessary for patients with severe dehydration, inability to maintain oral intake, significant electrolyte or metabolic abnormalities, severe systemic toxicity, HUS, seizures or encephalopathy, toxic megacolon, or other major complications.

One of the most important complications is hemolytic uremic syndrome, particularly associated with Shiga-toxin-producing S. dysenteriae type 1.

HUS is characterized by the classic triad of:

Microangiopathic hemolytic anemia + thrombocytopenia + acute kidney injury.

Neurologic manifestations, particularly seizures, can occur in young children with severe shigellosis. Fever, electrolyte abnormalities, hypoglycemia, and encephalopathy may contribute.

Severe colonic inflammation and tenesmus can occasionally cause rectal prolapse, particularly in young children.

Other gastrointestinal complications include toxic megacolon, intestinal obstruction, colonic perforation, and severe colitis, although these are uncommon.

A delayed complication is reactive arthritis, classically involving asymmetric arthritis of the lower extremities following gastrointestinal infection. Susceptibility has historically been associated with HLA-B27, although reactive arthritis can occur without it.

Prevention centers on meticulous hand hygiene, safe food preparation, adequate sanitation, safe drinking water, and preventing fecal contamination of food and environmental surfaces.

Because shigellosis is highly transmissible, infected individuals should avoid preparing food for others while infectious. Special occupational or return-to-childcare requirements may apply to food handlers, healthcare workers, childcare workers, and young children attending childcare, according to local public-health regulations.

Shigellosis is a notifiable disease in many jurisdictions, and suspected outbreaks require public-health involvement.

Most otherwise healthy patients recover completely. Prognosis becomes less favorable with severe dehydration, malnutrition, very young age, immunocompromise, HUS, encephalopathy, or severe colonic complications.

A useful clinical pattern to remember is:

Fecal–oral transmission + extremely low infectious dose → fever and watery diarrhea → bloody/mucoid small-volume stools + cramps + tenesmus = Shigellosis.

S. dysenteriae type 1 → Shiga toxin → HUS

Diagnosis → stool testing/culture + susceptibility testing when indicated

Treatment → rehydration first + selective susceptibility-guided antibiotics + avoid antimotility drugs in dysentery.

Infectious Disease and Microbiology – Septic Arthritis

Septic arthritis is infection of a joint resulting in acute inflammation of the synovium and joint space. Although bacteria are the most important causes of acute septic arthritis, infection may also be caused by mycobacteria, fungi, and occasionally viruses.

Septic arthritis is a medical and orthopedic emergency because rapidly progressive inflammation can cause irreversible destruction of articular cartilage. Prompt arthrocentesis, antimicrobial therapy, and adequate joint drainage are central to management.

The incidence in the general population is relatively low but increases substantially in patients with preexisting joint disease or prosthetic joints.

Important risk factors include advanced age, rheumatoid arthritis or other chronic joint disease, diabetes mellitus, immunosuppression, malignancy, recent joint surgery, prosthetic joints, intra-articular injections, skin infection, trauma, animal bites, and injection drug use.

Most bacterial septic arthritis results from hematogenous spread during bacteremia. Less commonly, organisms enter through direct inoculation following trauma, surgery, injection, or an animal bite, or by contiguous spread from an adjacent infection such as osteomyelitis.

Once organisms enter the joint, bacterial proliferation and the resulting intense inflammatory response can rapidly damage cartilage. Neutrophils, cytokines, bacterial toxins, and proteolytic enzymes all contribute to articular destruction.

Staphylococcus aureus is the most important and generally the most common cause of native-joint bacterial septic arthritis in adults. Both methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) must be considered.

Streptococci are also important causes. Group B Streptococcus is particularly associated with older adults and patients with underlying illnesses.

Gram-negative bacilli should be considered particularly in older adults, immunocompromised patients, people with urinary or gastrointestinal sources of bacteremia, and patients with healthcare-associated infection.

Pseudomonas aeruginosa has an important association with injection drug use, although other organisms can also occur. The sternoclavicular and sacroiliac joints are unusual sites that should raise suspicion for infection in this population.

Neisseria gonorrhoeae remains an important cause of septic arthritis in sexually active adolescents and young adults. Disseminated gonococcal infection can produce a characteristic syndrome of migratory polyarthralgia, tenosynovitis, and pustular skin lesions, with or without subsequent purulent monoarthritis.

Animal bites can directly inoculate joints. The microbiology depends on the animal and exposure; organisms such as Pasteurella multocida should be considered following cat or dog bites.

A chronic or indolent monoarthritis raises a different microbiologic differential. Important causes include Mycobacterium tuberculosis, nontuberculous mycobacteria, and fungi such as Coccidioides and Sporothrix in appropriate epidemiologic settings.

Patients usually present with acute joint pain, swelling, warmth, and marked limitation of movement. Fever is common but may be absent, particularly in older or immunocompromised patients.

The knee is the most frequently affected native joint, followed by other large joints such as the hip, shoulder, ankle, elbow, and wrist. Most cases are monoarticular, although polyarticular septic arthritis can occur, especially in patients with bacteremia, rheumatoid arthritis, or immunosuppression.

Both active and passive range of motion are usually extremely painful because the pathological process lies within the joint. This can help distinguish septic arthritis from some periarticular disorders such as bursitis or tendinitis.

In infants and young children, presentation can be less specific. Findings include irritability, refusal to move the affected limb (pseudoparalysis), limp, or inability to bear weight. Septic arthritis of the hip is particularly important because it may be difficult to recognize clinically.

The most important diagnostic procedure is urgent arthrocentesis with examination of synovial fluid. Whenever feasible, synovial fluid and blood cultures should be obtained before antibiotics are administered, provided this does not cause a clinically important delay in treatment.

Synovial fluid should generally be sent for cell count with differential, Gram stain, and bacterial culture. Crystal analysis should also be performed when gout or calcium pyrophosphate deposition disease is possible.

Typical bacterial septic arthritis produces turbid or purulent synovial fluid with a high leukocyte count and neutrophilic predominance. A synovial WBC count greater than approximately 50,000 cells/µL increases suspicion for infection, especially with a high proportion of neutrophils.

However, a synovial WBC count below 50,000 cells/µL does not exclude septic arthritis. Lower counts can occur early in infection, in immunocompromised patients, and with certain organisms.

Conversely, very high synovial leukocyte counts are not specific for infection because severe crystal-induced arthritis can produce similar findings. Finding monosodium urate or calcium pyrophosphate crystals also does not completely exclude concomitant septic arthritis.

Synovial-fluid Gram stain has limited sensitivity, so a negative Gram stain cannot rule out infection. Synovial-fluid culture has substantially greater diagnostic importance.

At least two sets of blood cultures should generally be obtained when septic arthritis is suspected, particularly when the patient is febrile or bacteremic. Blood cultures can identify the pathogen even when synovial cultures are negative.

Inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are frequently elevated. They are nonspecific and cannot independently confirm or exclude septic arthritis, but serial measurements can assist in assessing response to treatment.

Peripheral leukocytosis may occur but can also be absent. A normal peripheral WBC count therefore does not exclude joint infection.

When gonococcal infection is suspected, testing should include appropriate nucleic acid amplification tests (NAATs) from relevant genital and extragenital sites because synovial-fluid cultures may be negative.

Plain radiographs are useful as an initial study to identify underlying joint abnormalities, fractures, foreign material, or late destructive changes. Early findings may be limited to soft-tissue swelling and joint effusion.

Ultrasonography is particularly useful for identifying effusions in joints such as the hip and can guide aspiration.

MRI is highly useful when there is concern for associated osteomyelitis, deep soft-tissue infection, abscess, or difficult-to-assess joints, but imaging should not unnecessarily delay diagnostic aspiration of an accessible joint.

The major differential diagnosis includes gout, pseudogout, rheumatoid arthritis, reactive arthritis, traumatic hemarthrosis, osteoarthritis, bursitis, cellulitis, Lyme arthritis, and other inflammatory arthropathies.

Once appropriate cultures have been obtained, empiric intravenous antibiotics should be started promptly when clinical suspicion for bacterial septic arthritis is substantial.

Empiric therapy should generally provide coverage for S. aureus, including MRSA when appropriate, while additional gram-negative coverage is added according to the patient’s age, immune status, Gram-stain findings, exposure history, and local epidemiology.

A commonly used empiric approach for a seriously ill adult with a negative Gram stain is vancomycin plus a third- or fourth-generation cephalosporin, with the exact regimen adjusted to individual risk factors and local resistance patterns.

Once the organism and antimicrobial susceptibility results are known, treatment should be narrowed to targeted therapy. MSSA, for example, is generally better treated with an antistaphylococcal β-lactam such as cefazolin or nafcillin/oxacillin rather than continuing vancomycin when there is no relevant β-lactam contraindication.

The duration of treatment depends on the organism, affected joint, adequacy of drainage, presence of bacteremia or osteomyelitis, and clinical response. Many uncomplicated native-joint bacterial infections require several weeks of antimicrobial therapy, but treatment duration should be individualized rather than applying a fixed IV course to every patient.

Antibiotics alone are usually insufficient. Adequate drainage of the infected joint is a fundamental component of treatment.

Drainage may be accomplished through repeated needle aspiration, arthroscopic irrigation and drainage, or open surgical drainage. The optimal approach depends on the joint involved, amount and persistence of purulent material, organism, underlying joint anatomy, and clinical response.

Early orthopedic consultation is particularly important for hip or shoulder infection, difficult-to-drain joints, extensive infection, failure to improve, or infection involving a prosthetic joint.

Prosthetic-joint infection requires a separate management strategy combining antimicrobial treatment with decisions regarding debridement and implant retention, one-stage exchange, two-stage exchange, or removal of the prosthesis, depending on the clinical circumstances.

Septic arthritis should prompt assessment for the source of bacteremia and associated infections. In appropriate patients, clinicians should consider endocarditis, osteomyelitis, skin and soft-tissue infection, urinary infection, and other potential primary sources.

After adequate control of infection, physical therapy and progressive joint mobilization are important to preserve range of motion and function. Prolonged unnecessary immobilization can contribute to stiffness and functional impairment.

Clinical improvement is assessed through decreasing pain, swelling, fever, and inflammatory markers together with improved joint function. Persistent fever, recurrent effusion, continued bacteremia, or failure of CRP to decline should raise concern for inadequate drainage, resistant organisms, osteomyelitis, abscess, or another uncontrolled infectious focus.

Major complications include rapid cartilage destruction, joint-space narrowing, ankylosis, chronic pain, reduced range of motion, permanent joint dysfunction, osteomyelitis, sepsis, and death.

Children can additionally develop damage to the growth plate or epiphysis, potentially producing impaired limb growth or permanent deformity.

A useful clinical rule is:

Acute hot + swollen + very painful joint = septic arthritis until adequately excluded.

Do not rely on absence of fever, a normal blood WBC count, a negative Gram stain, or synovial WBC <50,000/µL to rule it out.

The core sequence is:

Urgent arthrocentesis → synovial Gram stain/culture + blood cultures → prompt empiric antibiotics → adequate joint drainage → culture-directed therapy.

Infectious Disease and Microbiology – Schistosomiasis

Schistosomiasis, also called bilharziasis, is a parasitic infection caused by blood flukes of the genus Schistosoma. Humans serve as definitive hosts, while specific freshwater snails serve as intermediate hosts.

The major species causing human disease are Schistosoma mansoni, S. haematobium, S. japonicum, S. mekongi, and S. intercalatum. The species differ geographically and in the organs predominantly affected.

S. mansoni occurs predominantly in sub-Saharan Africa, parts of the Middle East, South America, and some Caribbean regions. It primarily produces intestinal and hepatosplenic schistosomiasis.

S. haematobium is found mainly in Africa and parts of the Middle East. It predominantly involves the urinary tract and is particularly associated with hematuria, urinary obstruction, bladder-wall calcification, and an increased risk of squamous cell carcinoma of the urinary bladder.

S. japonicum occurs primarily in parts of China, the Philippines, and Indonesia, while S. mekongi occurs around the Mekong River region of Cambodia and Laos. These species primarily cause intestinal and hepatosplenic disease and can occasionally produce neurologic complications.

The major risk factor is skin contact with contaminated freshwater in an endemic region. Swimming, bathing, washing, fishing, or wading in freshwater can expose a person to infective cercariae.

Infected humans release schistosome eggs in urine or feces. When the eggs reach freshwater, they hatch and release miracidia, which infect susceptible freshwater snails.

Within the snail, the parasite develops and eventually produces free-swimming cercariae. Cercariae are released into freshwater and can directly penetrate intact human skin.

After penetrating the skin, cercariae lose their tails and become schistosomula. They enter the circulation, migrate through the lungs and liver, mature into adult male and female worms, and subsequently migrate to their characteristic venous sites.

Adult S. mansoni, S. japonicum, and S. mekongi principally inhabit the mesenteric venous system, whereas S. haematobium predominantly inhabits the vesical venous plexus surrounding the urinary bladder.

Adult worms can survive for many years. Much of the disease is not caused directly by the adult worms but by the host’s granulomatous inflammatory response to deposited eggs.

Some eggs penetrate the intestinal or bladder wall and leave the body in feces or urine. Other eggs remain trapped within tissues or embolize to organs such as the liver, lungs, brain, or spinal cord, producing chronic inflammation and fibrosis.

The earliest manifestation following skin penetration can be cercarial dermatitis, commonly called swimmer’s itch. Patients may develop an itchy, erythematous, papular or urticarial eruption at sites of cercarial penetration.

Acute schistosomiasis (Katayama syndrome) usually develops several weeks after initial infection, particularly in previously unexposed individuals. It represents a systemic hypersensitivity response associated with maturation of the worms and initiation of egg production.

Katayama syndrome may produce fever, chills, headache, malaise, myalgia, cough, abdominal pain, diarrhea, urticaria, lymphadenopathy, and hepatosplenomegaly. Marked eosinophilia is an important laboratory clue.

Chronic intestinal schistosomiasis can cause abdominal pain, diarrhea, and gastrointestinal bleeding. Persistent deposition of eggs in the intestinal wall produces granulomatous inflammation and, in some patients, polyps and fibrosis.

Chronic hepatosplenic disease occurs particularly with S. mansoni and S. japonicum. Eggs reaching the liver induce granulomas and progressive periportal fibrosis.

The classic hepatic lesion is Symmers “pipestem” fibrosis, characterized by extensive periportal fibrosis. Importantly, hepatocyte function can remain relatively preserved until advanced disease or additional hepatic pathology develops.

Progressive periportal fibrosis causes portal hypertension, which can lead to splenomegaly, ascites, collateral circulation, and esophageal or gastric varices. Variceal hemorrhage can be a life-threatening complication.

Pulmonary schistosomiasis can occur when eggs reach the pulmonary circulation, particularly in patients with severe portal hypertension. Chronic pulmonary vascular disease may eventually cause pulmonary hypertension and cor pulmonale.

Urinary schistosomiasis is classically caused by S. haematobium. The characteristic presentation is hematuria, particularly terminal hematuria, together with dysuria or other urinary symptoms.

Chronic urinary disease can cause inflammation, ulceration, fibrosis, ureteric strictures, hydronephrosis, bladder dysfunction, and eventually obstructive uropathy or renal impairment.

Long-standing S. haematobium infection is strongly associated with squamous cell carcinoma of the bladder. This is one of the most important long-term complications of urinary schistosomiasis.

Genital schistosomiasis can affect both sexes. In women, lesions may involve the vulva, vagina, cervix, uterus, or fallopian tubes. In men, the prostate, seminal vesicles, epididymis, testes, or other genital structures may be affected.

Neuroschistosomiasis results from ectopic deposition of eggs in the central nervous system. Cerebral disease may produce headache, seizures, or focal neurologic deficits, whereas spinal involvement can cause myelopathy, weakness, sensory abnormalities, and paralysis.

Diagnosis is traditionally established by demonstrating characteristic schistosome eggs in stool or urine. Because egg excretion can be intermittent or low in light infections, repeated specimens and concentration techniques can substantially increase diagnostic sensitivity.

For suspected S. haematobium infection, urine microscopy is particularly important. Egg excretion often peaks around midday, so appropriately timed urine collection can improve detection.

The morphology of the eggs helps identify the species:

S. mansoni → prominent lateral spine

S. haematobium → prominent terminal spine

S. japonicum → small lateral knob/inconspicuous spine

Serologic antibody testing can be particularly useful in travelers or patients with light infections when microscopy is negative. However, antibodies can remain detectable after cure, so serology generally cannot reliably distinguish active from previously treated infection.

Antigen-detection assays and molecular methods such as PCR can provide additional evidence of infection where available. Their availability and routine use vary by setting.

Eosinophilia is common, especially during acute infection, but its absence does not exclude schistosomiasis. Anemia may develop because of chronic blood loss or advanced disease.

Abdominal ultrasonography can demonstrate periportal fibrosis, splenomegaly, portal hypertension, and other hepatosplenic abnormalities. Urinary ultrasonography can demonstrate bladder abnormalities, hydroureter, or hydronephrosis.

Chronic S. haematobium infection may cause characteristic bladder-wall calcification on imaging. CT or MRI of the brain or spinal cord is indicated when neuroschistosomiasis is suspected.

The differential diagnosis depends on the clinical syndrome and includes other helminthic infections, malaria, visceral leishmaniasis, viral hepatitis, inflammatory bowel disease, urinary tract disorders, and other causes of eosinophilia, portal hypertension, or hematuria.

Praziquantel is the treatment of choice for essentially all major forms of schistosomiasis. Treatment is recommended for infected patients because adult worms can survive for years and continue producing eggs.

For S. mansoni and S. haematobium, the usual praziquantel regimen is a total dose of 40 mg/kg orally in one day, generally divided into two doses.

For S. japonicum and S. mekongi, a total dose of 60 mg/kg orally in one day, generally divided into three doses, is commonly used.

Praziquantel acts most effectively against mature adult worms and is less effective against immature schistosomula. Therefore, patients treated very early after exposure may require repeat treatment after the parasites have matured.

Repeat praziquantel treatment may also be considered when viable eggs continue to be detected after treatment or when infection is believed to persist. Follow-up stool or urine examinations can be used to document parasitologic response when eggs were initially detectable.

Corticosteroids may be required as adjunctive therapy in severe acute Katayama syndrome and are particularly important when significant neurologic schistosomiasis produces inflammatory CNS disease.

Advanced complications require specific management in addition to antiparasitic therapy. Portal hypertension and esophageal varices may require gastroenterologic management, while obstructive urinary disease may require urologic intervention.

Prevention depends primarily on avoiding unsafe freshwater exposure in endemic regions, improving sanitation, reducing contamination of freshwater with human urine and feces, controlling snail populations where appropriate, and population-level treatment programs in endemic communities.

The prognosis is generally good when infection is diagnosed and treated before irreversible organ damage develops. Advanced portal hypertension, pulmonary hypertension, obstructive uropathy, neurologic disease, or malignancy can substantially worsen long-term outcomes.

A useful clinical pattern to remember is:

Freshwater exposure → cercarial skin penetration → eosinophilia/Katayama fever → egg deposition → chronic organ-specific disease.

S. mansoni / S. japonicum → intestine + liver → periportal “pipestem” fibrosis → portal hypertension

S. haematobium → urinary bladder → hematuria + calcification → squamous cell carcinoma

Infectious Disease and Microbiology – Scarlet Fever

Scarlet fever is a toxin-mediated illness caused by group A Streptococcus (GAS), Streptococcus pyogenes. It is characterized by an erythematous, finely papular rash associated most commonly with streptococcal pharyngitis. The rash results from streptococcal pyrogenic (erythrogenic) exotoxins.

Scarlet fever occurs predominantly in children, particularly school-aged children, and is uncommon in adults. Its epidemiology generally parallels that of group A streptococcal pharyngitis, with infections occurring most frequently during late fall, winter, and early spring in temperate climates.

Transmission usually occurs through respiratory droplets and close contact with an infected person. Household contacts, classmates, roommates, and people living in crowded environments therefore have increased exposure.

Although pharyngitis is the classic underlying infection, toxin-producing GAS infections at other sites can occasionally produce a scarlet-fever syndrome. These include infected wounds, burns, skin infections, surgical wounds, and puerperal infections.

Scarlet fever develops when an infecting strain of GAS produces streptococcal pyrogenic exotoxins in a susceptible host. These exotoxins are responsible for the characteristic rash and other systemic manifestations.

The incubation period is usually a few days. Illness commonly begins abruptly with fever and sore throat. Associated manifestations can include chills, headache, malaise, myalgia, nausea, vomiting, and abdominal pain, particularly in children.

Examination of the throat commonly demonstrates erythematous pharyngitis or tonsillitis, sometimes with tonsillar exudates. Palatal petechiae may be present, and tender anterior cervical lymphadenopathy is common.

The characteristic rash generally appears within the first few days of illness. It usually begins on the neck, upper chest, or trunk and subsequently spreads to the remainder of the trunk and extremities.

The rash consists of numerous small erythematous papules that produce the classic fine “sandpaper” texture. It typically blanches with pressure. The palms and soles are usually spared during the initial exanthem.

The face may appear flushed, but the region immediately surrounding the mouth characteristically remains pale. This finding is known as circumoral or perioral pallor.

Another characteristic finding is Pastia’s lines. These are areas of accentuated erythema within skin folds, particularly in the antecubital fossae, axillae, and groin. They result from increased concentration of the rash and petechiae in flexural areas.

The tongue may initially have a white coating with prominent erythematous papillae, producing the appearance traditionally called a white strawberry tongue. After several days, the coating disappears and the tongue becomes intensely erythematous with prominent papillae—the classic red strawberry or raspberry tongue.

The exanthem generally resolves within approximately a week. As the rash fades, desquamation may occur. Peeling can persist for several weeks and may become particularly noticeable around the fingertips, toes, hands, and feet.

Diagnosis is based on the compatible clinical syndrome together with evidence of group A streptococcal infection. Because several illnesses can produce a scarlatiniform rash, microbiologic confirmation of GAS pharyngitis is important when appropriate.

A rapid antigen detection test can identify GAS from a throat specimen. A throat culture can also establish the diagnosis and is particularly useful when additional confirmation is required. Current testing strategies depend on the patient’s age and local clinical guidelines.

Leukocytosis may occur during acute disease, but routine blood counts are not required to establish uncomplicated scarlet fever. Antistreptococcal antibody tests such as antistreptolysin O (ASO) and anti-DNase B reflect previous streptococcal exposure and are generally more useful for evaluating delayed post-streptococcal complications than for diagnosing acute pharyngitis.

The differential diagnosis includes viral exanthems, drug eruptions, Kawasaki disease, toxic shock syndrome, staphylococcal toxin-mediated disease, measles, rubella, and other causes of a diffuse erythematous rash. Clinical context and microbiologic testing help distinguish these disorders.

Penicillin or amoxicillin is standard first-line treatment for uncomplicated GAS pharyngitis associated with scarlet fever. A conventional oral penicillin or amoxicillin course is generally given for 10 days.

Appropriate alternatives are available for patients with penicillin allergy, with the choice depending partly on whether the allergy represents immediate hypersensitivity. Options can include selected cephalosporins, clindamycin, azithromycin, or clarithromycin. Local macrolide and clindamycin resistance should be considered when selecting therapy.

Antibiotic treatment shortens the period of contagiousness, reduces transmission, improves symptoms, and—when appropriately administered for GAS pharyngitis—helps prevent acute rheumatic fever.

Patients should receive adequate fluids, rest, and symptomatic treatment for fever and throat discomfort when necessary. Severe systemic illness, hemodynamic instability, rapidly progressive soft-tissue infection, or multisystem involvement should raise concern for invasive GAS infection or streptococcal toxic shock syndrome rather than uncomplicated scarlet fever.

Patients with uncomplicated scarlet fever generally become substantially less contagious after at least 12–24 hours of appropriate antibiotic therapy and when clinically improving. Good hand hygiene, respiratory etiquette, and avoidance of sharing eating utensils can help limit household and school transmission.

The prognosis is excellent with appropriate antibiotic treatment. The fever, pharyngitis, and rash usually resolve without permanent consequences, although skin desquamation can continue after the systemic illness has resolved.

Suppurative complications of the underlying GAS infection can include peritonsillar or retropharyngeal abscess, cervical lymphadenitis, otitis media, mastoiditis, pneumonia, bacteremia, and other invasive infections.

Important delayed immune-mediated complications include acute rheumatic fever and post-streptococcal glomerulonephritis. Acute rheumatic fever typically develops several weeks after GAS pharyngitis, whereas post-streptococcal glomerulonephritis may follow either pharyngeal or certain skin infections.

A useful clinical pattern to remember is:

GAS pharyngitis + fever → sandpaper-like rash → Pastia’s lines + circumoral pallor + strawberry tongue → later desquamation = Scarlet fever.

Infectious Disease and Microbiology – Scabies

Scabies is a contagious skin infestation caused by the human itch mite, Sarcoptes scabiei var. hominis. The condition is characterized primarily by intense itching and a characteristic skin eruption caused by infestation and the host immune response to the mite.

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Scabies occurs worldwide and affects people of all ages, sexes, ethnicities, and socioeconomic groups. Historically, hundreds of millions of cases have been estimated globally each year. The disease is particularly common in areas with overcrowding, limited access to healthcare, and resource-constrained living conditions.

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Individuals living in institutions, crowded households, shelters, or other settings involving prolonged close contact have an increased risk of transmission. Immunocompromised individuals and frail or institutionalized older adults are particularly susceptible to severe forms of infestation.

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Crusted scabies, previously called Norwegian scabies, is a severe form characterized by an extremely high mite burden. It is particularly associated with impaired cellular immunity and other conditions that reduce the ability to scratch or mount an effective immune response. Reported risk factors include immunosuppression, corticosteroid therapy, HTLV-1 infection, malnutrition, Down syndrome, and certain neurologic or cognitive conditions.

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Prevention requires prompt identification and treatment of affected individuals and their close contacts. Household members and other individuals with prolonged skin-to-skin contact should generally be managed simultaneously to prevent reinfestation.

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Clothing, towels, and bedding recently used by an affected person should be appropriately cleaned, usually by hot washing and hot drying. Items that cannot be washed can be isolated according to appropriate infection-control recommendations. Avoiding prolonged direct skin contact with an untreated infected person also reduces transmission.

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Scabies is primarily transmitted through prolonged direct skin-to-skin contact. Transmission through contaminated clothing, bedding, or other fomites is less common in ordinary scabies but becomes considerably more important in crusted scabies because of the very large number of mites present.

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After reaching the skin, fertilized female mites burrow into the superficial epidermis and deposit eggs. The eggs hatch into larvae, which subsequently develop into nymphs and adult mites.

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During a person’s first infestation, symptoms commonly take several weeks to develop because manifestations depend largely on sensitization to the mites and their products. In previously infected individuals, symptoms may develop within only a few days after reinfestation.

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The characteristic symptom is intense generalized pruritus, which is typically worse at night. Other household members or close contacts experiencing similar nocturnal itching can provide an important diagnostic clue.

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Typical examination findings include erythematous papules, excoriations from scratching, and thin linear or serpiginous burrows. Common locations include the interdigital spaces of the fingers, flexor surfaces of the wrists, elbows, axillae, periumbilical region, waistline, buttocks, genital region, breasts, ankles, and feet.

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In healthy adults, the head, face, and neck are usually spared. However, infants, young children, older adults, and immunocompromised patients may develop involvement of the scalp, face, neck, palms, or soles.

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Nodular scabies presents with persistent, intensely pruritic reddish-brown or violaceous nodules, particularly around the genital region, groin, and axillae. These lesions may persist even after the mites have been successfully eradicated because of continued hypersensitivity.

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Crusted scabies has a different appearance from classic scabies. Patients develop extensive hyperkeratotic, crusted, or psoriasiform plaques that may involve the hands, feet, nails, scalp, face, or other large areas of the body. Because these patients can harbor enormous numbers of mites, crusted scabies is extremely contagious.

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Diagnosis is often made clinically from the combination of characteristic itching, distribution of lesions, burrows, and an appropriate exposure history. Confirmation can be obtained by demonstrating mites, eggs, or fecal material from a skin scraping examined microscopically.

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Dermoscopy can assist diagnosis by allowing direct visualization of characteristic structures associated with the mite and its burrow. Videodermoscopy may provide greater magnification. Skin biopsy is rarely required but can be useful when the presentation is atypical and the diagnosis remains uncertain.

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The differential diagnosis includes eczema, contact or atopic dermatitis, drug eruptions, pediculosis corporis, dermatitis herpetiformis, lichen planus, pityriasis rosea, papular urticaria, and other pruritic dermatoses.

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Permethrin 5% cream is a standard first-line treatment for classic scabies. It is generally applied thoroughly over the recommended body surface, commonly from the neck downward in adults, and left in place for approximately 8–14 hours before being washed off. Treatment is commonly repeated after about one week because the initial application may not eliminate all newly developing mites.

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Application must include easily overlooked areas such as between the fingers and toes, underneath the fingernails, around the umbilicus, buttocks, groin, and external genital region. In infants, older adults, and some immunocompromised patients, treatment may also need to include the scalp and other areas above the neck while avoiding the eyes and mouth.

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Oral ivermectin is another important treatment option and is especially useful for outbreaks, treatment failure, difficulty applying topical therapy, or crusted scabies. A commonly used regimen is 200 micrograms/kg orally, with a second dose approximately 7–14 days later. Multiple doses combined with topical therapy are generally required for crusted scabies.

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Other topical treatments include sulfur preparations and, depending on local availability, benzyl benzoate or crotamiton. Sulfur preparations have historically been useful when treatment options are limited, including in certain very young infants or during pregnancy. Treatment selection should take age, pregnancy, comorbidities, availability, and local recommendations into account.

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Lindane has historically been used as an alternative scabicide but is now generally avoided or restricted because systemic absorption can cause serious neurotoxicity, including seizures. Safer alternatives are preferred whenever available.

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Close contacts should generally be treated at the same time as the affected patient, even when they do not yet have symptoms, because the incubation period can be several weeks. Failure to treat contacts is an important cause of apparent treatment failure and recurrent infestation.

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Recently used clothing, towels, and bedding should be cleaned at the time treatment begins. Environmental cleaning is particularly important in crusted scabies. Routine excessive cleaning or pesticide treatment of the entire home is generally unnecessary for ordinary scabies.

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Antihistamines and other symptomatic treatments may help control itching. Importantly, pruritus can continue for several weeks after successful eradication because the inflammatory and hypersensitivity response does not disappear immediately.

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Persistent itching shortly after treatment therefore does not necessarily indicate treatment failure. Reassessment is appropriate when symptoms continue, worsen, new burrows or characteristic lesions appear, treatment was applied incorrectly, or untreated contacts could have caused reinfestation.

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Patients with crusted scabies require particularly careful management because of their high mite burden, infectiousness, and association with underlying immunosuppression or debilitating disease. Dermatology or infectious-disease consultation may be appropriate, and infection-control precautions are especially important in institutional outbreaks.

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The prognosis of uncomplicated scabies is excellent with appropriate therapy. Treatment failures are most often related to incorrect application, inadequate treatment of contacts, reinfestation, or failure to recognize crusted scabies rather than true resistance.

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The most important complication is secondary bacterial infection of excoriated skin, particularly with Staphylococcus aureus or Streptococcus pyogenes. Scabies can also exacerbate preexisting eczema and, in heavily affected populations, secondary streptococcal skin infection can contribute to more serious postinfectious complications.