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8 Systemic, Infectious, andInammatory Diseases

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• Histologic signs

– Mikulicz cells—vacuolated, large macrophage with clear cytoplasm that con-

tains bacilli – Large foamy histiocytes – Russell bodies—eosinophilic, large, immunoglobulin-containing inclusions

found in plasma cells

• Stages

– Catarrhal: foul-smelling purulent rhinorrhea lasting weeks to months – Atrophic: large foul crusts simulating atrophic rhinitis – Granulomatous: large granulomas of the upper respiratory tract – Fibrosis: progressive stenosis of nares, with possible involvement of naso-

pharynx and trachea

• Treatment: debridement, long-term streptomycin and tetracycline, supportive airway management

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Cat Scratch Disease

Caused by Bartonella (aka Rochalimaea) henselae, intracellular pleomorphic gram- negative bacillus, visible on Warthin-Starry silver staining. Reservoir for Bartonella is kittens; vector is cat ea.

• Diagnosis: history of exposure to cats, papule/pustule 1–2weeks after exposure, local lymphadenopathy; 10–30% spontaneously suppurates. Cultures require 6-week incubation period. Test for antibodies to B. henselae

• Atypical presentation: Parinaud’s oculoglandular syndrome—unilateral granulomatous conjunctivitis, associated with ipsilateral pre-auricular or submandibular lymphadenopathy. Bacillary angiomatosis—cutaneous proliferative vascular lesions

• Treatment: reassurance, self-limiting spontaneously resolving disease in 1–2months; rifampin, azithromycin, not beta-lactams

Tuberculosis

Acid-fast bacilli, mycobacterium tuberculosis, leading cause of death in HIVpositive patients

• Head and neck manifestations

– Cervical lymphadenopathy (scrofula), most commonly anterior superior cer-

vical region followed by posterior cervical. With overlying skin changes. Commonly seen in HIV-positive patients

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– Otitis media (0.05–0.9%) with lymphadenopathy in high jugular chain – Larynx—involvement of vocal folds, ventricular folds, aryepiglottic folds,

posterior glottis

– Salivary glands—may become encapsulated in intraglandular lymph nodes of

parotid gland. Rarely involves facial nerve

– May present as acute inammatory lesion with diffuse glandular edema

(could be confused with sialadenitis)

– May present as chronic, slow-growing mass that mimics neoplasm

• Diagnosis: cultures positive for AFB.Test for HIV.FNA demonstrates granulomatous inammation and epithelioid histiocytes. Calcication on CT

• Treatment: anti-tuberculous medication, incision and drainage versus excision of LAD with abscess, depending on location

A. M. Roche and Z. M. Patel

Leprosy (Hansen’s Disease)

• Mycobacterium leprae, aerobic, intracellular, pleomorphic acid-fast bacilli, transmitted by aerosolized droplets, can be highly contagious, though only 5–10% develop disease. Difcult to culture exvivo, cultured in armadillos

• Diagnosis: skin and peripheral nerve involvement. Painless, insensate skin patches. Tissue staining shows acid-fast bacilli and granuloma formation. Hypercalcemia

• Head and neck manifestations: in disseminated disease, >1/3 have laryngeal involvement; laryngeal and upper tracheal stenosis. Rhinitis

• Treatment: dapsone, rifampin, clofazimine for 1–2years

Histoplasmosis

Dimorphic fungus Histoplasma capsulatum, in Ohio and Mississippi River Valley. Exists in soil in mycelial form, converts to yeast when exposed to higher temperature (human body). Can present as acute or chronic pulmonary infection or an acute or chronic disseminated infection with systemic symptoms. Is an AIDS-dening illness. Oral histoplasmosis lesions strongly associated with HIV/AIDS, CD4 <50cells/μL

• Presentation: acute pulmonary, chronic pulmonary, or disseminated infection. If disseminated, at, plaque-like, nontender elevation, become tender after ulceration, can resemble squamous cell carcinoma or TB.

• Oral lesions: painful erythematous patches that progress to raised, granulomatous lesions covered with pseudomembrane, may have cervical adenopathy.

• Larynx: hoarseness, aspiration, dysphagia.

8 Systemic, Infectious, andInammatory Diseases

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• Otologic: via ascending infection along Eustachian tube, superinfection of existing chronic otitis media, or hematogenous embolic dissemination. Granulomas of temporal bone.

• Diagnosis: tissue biopsy shows poorly dened granulomas with macrophages and multinucleated giant cells on H&E stains. Wright-Giemsa or methenamine silver stain shows macrophages with intracellular oval and round bodies (fungi in yeast form).

• Treatment: amphotericin B × 1–2 weeks, itraconazole prophylaxis if CD4 <150cells/μL or other immunosuppression and with recurrent disease.

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Blastomycosis

Caused by dimorphic fungus Blastomyces dermatitidis. Endemic in Mississippi and Ohio River basins. Primary point of entry is the lungs. Hematogenous spread (including laryngeal involvement)

• Presentation: Skin most common system involved. Larynx involved 2%—manifest with hoarseness. True vocal folds most common subsite with extension into ventricular folds—exophytic lesions or ulcerative lesions. Must biopsy.

• Histologic ndings: acute and chronic inammation, microabscesses, giant cell formation; pseudoepitheliomatous hyperplasia is hallmark nding.

• Diagnosis: fungal stain on Gomori methenamine silver shows double-walled sphere, 8–15mm diameter, broad-based buds.

• Treatment: prolonged oral ketoconazole or itraconazole. Amphotericin B with CNS involvement.

Cryptococcosis

Caused by Cryptococcus neoformans, yeast-like fungus with thick polysaccharide capsule, found in pigeon dropping-contaminated areas. Contracted via spore inhalation

• Presentation: Subclinical presentation in immunocompetent patients. Immunocompromised—systemic infection, usually CNS meningitis, fever, fatigue, chest pain, dry cough, headache, blurry vision. Rare laryngeal involvement—hoarseness, true vocal fold involvement

• Diagnosis: cryptococcal antigen in culture of CSF, sputum, and/or urine. India ink stain. Biopsy of glottic lesion—budding yeasts, may see pseudoepitheliomatous hyperplasia

• Treatment: amphotericin B+ucytosine/uconazole

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A. M. Roche and Z. M. Patel

Coccidioidomycosis

San Joaquin Valley fever, caused by Coccidioides immitis, endemic to Southwest USA and Mexico. Contracted via spore inhalation

• Presentation: 40% develop u-like symptoms 1–3weeks after infection. Sixty percent of infections unrecognized. Larynx site of inoculation in some patients— hoarseness, odynophagia, stridor

• Diagnosis: culture from sputum, involved tissue biopsy, DNA detection of C. immitis, fungal antigen, or host antibody

• Treatment: amphotericin B

Candidiasis

Caused by Candida albicans, a diploid fungus that grows as yeast and lamentous cell. Infection usually in immunocompromised patients but can be indicative of systemic or localized immune compromise (steroid inhalers). Most common opportunistic infection of oral cavity, oropharynx, oral commissures, isolated laryngeal involvement with inhaled steroid use, associated with failure of tracheoesophageal puncture voice prosthesis

• Presentation—six clinical forms:

– Pseudomembranous candidiasis (thrush, classic presentation)—white sessile

(curd-like) plaques on erythematous base, plaques can be scraped off

– Acute atrophic candidiasis—antibiotic sore mouth, associated with broad-

spectrum antibiotic use, burning sensation in mouth, atrophy of dorsal lingual papillae

– Chronic atrophic candidiasis (most common)—erythematous, associated

with dentures/oral appliance, in distribution of appliance

– Hyperplastic candidiasis (increased epithelial atypia and malignant transfor-

mation), “candida leukoplakia,” rarest type, involves buccal mucosa along occlusal line, raised white plaques that cannot be scraped off

– Median rhomboid glossitis—“central papillary atrophy,” rhomboid area of

atrophy with associated corresponding palatal area of atrophy, satellite/kissing lesions

– Mucocutaneous candidiasis—angular cheilitis, tender and erythematous s-

sures and ulcers at oral commissure, superimposed bacterial infection with

S. aureus

• Risk factors: xerostomia, inhaled steroids, heavy smoking, poorly controlled diabetes, oral foreign bodies (e.g., dentures).

• Diagnosis: clinical presentation sufcient to initiate treatment; mucosal surface scraping and KOH placement, or tissue prep with periodic acid-Schiff (PAS) or methenamine silver. Can culture on Sabouraud medium.

8 Systemic, Infectious, andInammatory Diseases

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• Treatment: topical nystatin, PO uconazole, and “magic mouthwash” may help alleviate symptoms as well as treat infection.

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Diphtheria

Caused by Corynebacterium diphtheriae, gram-positivefacultative anaerobe, produces diphtheria toxin

• Presentation: sore throat, low-grade fever, dysphagia, odynophagia, dysphonia, cervical lymphadenopathy, pseudomembrane on tonsil, pharynx, and/or nasal cavity, associated myocarditis in 20%, peripheral neuropathy 10%. Contagious, aerosolized particles

• Diagnosis: isolate organism on gram stain or throat culture; Albert’s Stain

• Treatment: airway management, diphtheria antitoxin (does not neutralize toxin already bound to tissue), metronidazole, erythromycin PO/IV×14days, penicillin G IM×14days

Lemierre’s Syndrome

Typically caused by Fusobacterium necrophorum, internal jugular vein thrombophlebitis. Spread via tonsillar veins to internal jugular system; bacteria endotoxin causes platelet aggregation.

• Presentation: initial presentation of pharyngitis, lateral neck tenderness, otalgia; blood-stained, foul-smelling otorrhea; spiking fever (“picket fence”); engorged optic disks; increased CSF pressure; SCM tenderness; neck stiffness; metastatic lung abscesses; septic arthritis

• Diagnosis: CT neck with contrast, Griesinger’s sign—erythema and edema over mastoid process, Queckenstedt (Toby-Ayer) test—measuring CSF pressure with LP while compressing one or both IJVs. If no change/slow change in ICP, likely thrombosis. Normal IJV—rapid rise in ICP

• Treatment: rst line—beta-lactamase-resistant antibiotics+/−heparin, drainage of infection, ligation of IJV, anticoagulation controversial

Ludwig’s Angina

Rapid, gangrenous cellulitis involving all three primary spaces of the oral cavity (spaces where infection spreads from teeth to bone): sublingual, submandibular, and submental spaces bilaterally; typically extends posteriorly to involve secondary spaces causing trismus: masseteric, pterygomandibular, and temporal spaces; usually polymicrobial: Streptococcus viridans and oral anaerobes of odontogenic origin

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• Symptoms: trismus; drooling; tachypnea; oor of mouth, submental, and submandibular swelling; tachycardia; dysphagia; eventual airway distress secondary to posteriorly displaced tongue

• Treatment: airway control, incision and drainage of abscess/phlegmon. Broadspectrum aerobic and anaerobic antibiotic coverage to include MRSA, IV clindamycin in penicillin-allergic patients

A. M. Roche and Z. M. Patel

Necrotizing Fasciitis

Deep neck space infection, occurs more often in older patients (>60 years old), immunocompromised, poorly controlled diabetes. Origin commonly odontogenic, mixed ora—aerobes and anaerobes

• Presentation: progressive cellulitis, pitting neck edema, orange peel appearance secondary to obstructed dermal lymphatics +/− crepitus; CT neck with contrast—subcutaneous emphysema, diffuse loculated hypodense areas without rim-enhancement consistent with liquefactive necrosis

• Treatment: broad-spectrum IV antibiotics: piperacillin-tazobactam (or carbapenem)+vancomycin (or daptomycin) for MRSA coverage+clindamycin; intensive care and airway securement; surgical exploration and debridement of necrotic tissue until tissue bleeds, irrigate, pack with moist dressing, second look procedure in 2–3 days; adjuvant hyperbaric oxygen. Mortality of 20–30% in treated patients

Epstein-Barr Virus

Double-stranded capsid DNA in Herpesviridae family, remains latent in B lymphocytes; 80–90% people worldwide are seropositive; causative agent in infectious mononucleosis, implicated in nasopharyngeal carcinoma, Burkitt’s lymphoma, oral hairy leukoplakia, sensorineural hearing loss

• Infectious mononucleosis (IM): virus replicates in oropharyngeal epithelial cells and is transmitted via saliva, incubation period of 3–7weeks; prodrome of fever, malaise, chills; followed by sore 1–2weeks sore throat, fever, cervical adenopathy.

• Symptoms: erythematous and enlarged tonsils with exudates, diffuse hyperplasia of Waldeyer’s ring, petechiae at hard-soft palate junction, splenomegaly, hepatomegaly, peri-orbital edema. Presence of atypical lymphocytes on blood smear, symptoms caused by robust cytotoxic T-cell response. Diagnose with monospot test (detects presence of heterophile antibodies).

• Complications include secondary bacterial infection—group A beta-hemolytic Streptococcus in 30%, Guillain-Barré in 1–5%, cranial nerve VII neuropathy, spontaneous splenic rupture, hemolytic anemia.

8 Systemic, Infectious, andInammatory Diseases

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• Treatment: supportive care, avoid contact sports, antibiotics for secondary bacterial infection though avoid ampicillin/amoxicillin—causes maculopapular rash in patients with IM.

• Nasopharyngeal carcinoma (NPC): not all patients with EBV develop NPC.IgA antibodies to viral capsid antigen (VCA) and nuclear core early antigen most specic tests for diagnosis, titers ~85% positive in cases of WHO II and III NPC.Antibody-dependent cellular cytotoxicity (ADCC) titers: can be used to predict prognosis of WHO II and III NPC, signicant relationship between lower titers and progression—lower titers correlate with poorer prognosis.

• Burkitt’s lymphoma: non-Hodgkin’s lymphoma, high incidence in children in equatorial Africa and Brazil, Burkitt’s accounts for 50% of these, associated with EBV.Translocation of myc gene on chromosome 8 to chromosome 14.

• Histology: “starry sky,” characterized by homogenous small non-cleaved cells with minimal variability in nuclei size and shape.

• Symptoms: primarily in abdomen in patients in Africa, in head and neck in patients in the USA.

• Treatment: chemotherapy and CNS prophylaxis (intrathecal methotrexate and ara-C). Tumor lysis syndrome common; do not give steroids.

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Herpes Simplex Virus (HSV)

• Double-stranded DNA virus in Herpesviridae, HSV 1 and HSV 2. HSV 1 more often associated with head and neck pathology

• Causative agent in primary herpetic gingivostomatitis, pharyngitis, laryngitis, sensorineural hearing loss, herpes labialis (cold sore—indication of reactivation, not primary infection), and oral ulcerations. In oral ulcerations, high concentration of virus present in ulcers in rst few days, small round ulcers without erythematous halo, multinucleated giant cells seen in a Tzanck smear

• Treatment: initiate as soon as symptomatic, topical or oral acyclovir

Varicella-Zoster Virus (VZV)

Human herpes virus 3, member of Herpesviridae family. Initial infection results in “chicken pox”; virus lies dormant in sensory ganglia; reactivation presents with dermatomal distribution (“shingles”).

• Symptoms: in head and neck region, reactivation causes unilateral painful vesicles on skin or in oral cavity, distributed in ophthalmic, maxillary, or mandibular divisions of trigeminal sensory nerves. If ear involved (herpes-zoster oticus), vesicles in canal and conchal bowl, virus thought to be harbored in geniculate ganglion and spreads along sensory bers of CN VII.Can result in blindness (V1 distribution), facial paralysis/paresis (Ramsay Hunt syndrome), vertigo, and hearing loss

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• Treatment: antivirals (i.e., acyclovir, valacyclovir), analgesia, high-dose steroids for sensorineural hearing loss and facial paralysis

A. M. Roche and Z. M. Patel

Human Papilloma Virus (HPV)

Member of Papillomaviridae family, over 200 types, HPV 6 and 11 causative agents in recurrent respiratory papilloma and genital condyloma. HPV 16, and 18 causative agents in most squamous cell carcinoma of the head and neck and cervix

• Treatment modalities for recurrent respiratory papillomatosis (RRP)

– Tracheostomy associated with increased risk of distal spread, avoid unless

absolutely necessary

– Surgical debulking the standard of care: remove as much disease as possible

while preserving normal structures. Modalities include CO2 laser, KTP laser; microlaryngoscopy with cold knife or microdebrider; cryosurgery

– Adjuvant therapy: 20% of patients will require some form; criteria include >4

surgeries/year, distal multisite spread of disease, rapid regrowth with airway compromise. Modalities include cidofovir (use discouraged in children), Avastin (bevacizumab)—newer agent, monoclonal antibody inhibits VEGF- A; interferon therapy, autogenous vaccine, Indole-3-carbamol diet supplementation (found in cruciferous vegetables), ribavirin (used in RSV pneumonia, some promise), mitomycin C, mumps vaccine (some promise), antireux therapy

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2, “COVID-19”)

• Enveloped single-stranded RNA virus

• Cause of 2019 pandemic, originating in Wuhan, China

• Diagnosis: clinical, nasopharyngeal, nasal and oropharyngeal swab for viral titers

• Symptoms include:

– Fever – Nonproductive cough – Shortness of breath – Anosmia/hyposmia/parosmia – Headache – Sore throat – Myalgias

• Treatment: supportive care, isolation, ventilator support in severe cases but avoid ventilation and tracheostomy unless absolutely necessary, nirmatrelvir co-packaged with ritonavir (Paxlovid), oral anti-viral

8 Systemic, Infectious, andInammatory Diseases

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Osteodystrophies

Fibrous Dysplasia

Genetically based developmental anomaly, defect in osteoblastic differentiation, replacement of normal medullary bone by brous tissue and immature woven bone. Presents <age 30, lesions present as painless enlarging bony swelling. Twenty-ve percent occurs in head and neck, mainly maxilla

• Three clinical presentations

– Monostotic (80%), most commonly in ribs and femur – Polyostotic (17%) – Disseminated (McCune-Albright syndrome) (3%): polyostotic disease associ-

ated with triad of hyperpigmentation, precocious puberty, and endocrinopathy

• Histology: not encapsulated (versus ossifying broma, which has a capsule), immature bone without osteoblastic activity

• Symptoms: sinonasal obstruction and associated pain; if compressing optic nerve, diplopia, aesthetic deformity

• Workup: computed tomography—ndings depend on density of mineralization— in early disease higher density of brous tissue, appears radiolucent or lytic, similar to bone cyst. As disease progresses, ground-glass appearance. MR imaging— hypointense on T1, variable ndings T2, nonhomogeneous after gadolinium

• Treatment (only for cosmetic deformity, or impingement of critical structures causing pain or functional decit): surgical debulking, curettage, and excision. Medical management with bisphosphonates (pamidronate, zoledronate) to inhibit osteoclastic activity. Radiotherapy contraindicated due to possible malignant conversion

Ossifying Fibroma

Benign neoplasm. Occurs in third to fourth decade, more common in black females, psammomatoid variant occurs in men at younger age, more aggressive

• Histology: encapsulated, variant with small ossicles in stroma that appear like psammoma bodies

• Symptoms: space occupying lesion in nasal cavity, temporal bone

• Workup: endoscopic exam—lesion covered by intact mucosa. Computed tomography—well-dened, multiloculated lesion, bordered by egg-shell-like rim. MR imaging—hyperintense on T2; on T1 central portion intermediately to hyperintense central portion with hypointense outer portion

• Treatment: surgical radical resection due to high rate of aggressive recurrence with local destructive potential. Radiotherapy contraindicated due to possible malignant conversion

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A. M. Roche and Z. M. Patel

Paget’s Disease

Osteitis deformans, idiopathic chronic and at times progressive disease of bone, osteolytic, and osteoblastic changes that affect axial skeleton. Autosomal dominant pattern with high penetrance, associated with mutations in gene-encoding sequestosome 1, possibly related to viral infection. Age of onset >40, polyostotic most common, occurs in the lumbar spine, head and neck; skull and maxilla often involved

• Three phases of disease

– Osteolytic phase – Mixed or combined phase – Osteoblastic “burnout” phase

• If temporal bone involvement—remodeling of inactive irregular bone into normal appearing lamellar bone

• Symptoms: enlarging head, kyphosis. If inner ear and/or internal auditory canal involved, tinnitus, mixed hearing loss (50%) vestibular dysfunction. Facial nerve spared. Spacing and mobility of teeth if maxilla involved

• Histology: osteoclastic resorption, increased vascularity and formation of brous tissue, mosaic pattern of new bone formation

• Workup/diagnosis: elevated serum alkaline phosphatase, thickened skull table, lytic lesions in calvarium

• Treatment: calcitonin, bisphosphonates (inhibit osteoclasts)