●The current drug of choice for children or pregnant women is parenteral ceftriaxone (50–80 mg/kg qd for 5–7 days). Quinolone use has been shown experimentally to damage cartilage in young animals and should probably be avoided in these patients.

●Third generation cephalosporins and azithromycin are useful for drug-resistant strains.

●Patients in shock or with altered mental status may benefit from corticosteroid administration, usually parenteral dexamethasone (3 mg/kg followed by 1 mg/kg every 6 hours for 48 hours).

●Supportive care, consisting of intravenous fluids and occasionally transfusion, is often required. The use of aspirin is relatively contraindicated due to reported hypothermia, hypotension and gastrointestinal mucosal irritation.

REFERENCES

Bajpai PC, Dikshit SK: Bilateral optic neuritis and encephalitis complicating typhoid fever. J Indian Med Assoc 30:54–57, 1958.

Dhir SP, Jain IS, Kumar P, et al: Salmonella lid abscess. Indian J Ophthalmol 24:27–28, 1977.

Duke-Elder S: Typhoid fever. In: Duke-Elder S, ed: System of ophthalmology, (summary of systemic ophthalmology). St Louis, CV Mosby, 1976: XV:163–164.

Fusco R, Magli A, Guacci P: Stellate maculopathy due to Salmonella typhi: a case report. Ophthalmologica, Basel 192:154–158, 1986.

Keusch G: Salmonellosis. In: Fauci AS, et al, eds: Harrison’s principles of internal medicine. 14th edn. New York, McGraw-Hill, 1998:950– 956.

Lewis PJ, Jones BL: Vitreous haemorrhage after typhoid cholera inoculation. Med J Aust 2:914, 1974.

the initial infection, although the choice of antibiotic should ideally be guided by sensitivity. It may be reasonable to use ciprofloxacin or ceftriaxone if not used initially.

●Treatment of the chronic carrier state is difficult as anatomical abnormalities are often present (e.g. biliary or renal stones). Most clinical experience has involved amoxicillin

or trimethoprim-sulfamethoxazole; eradication rates of >80% are reported following 6 weeks of therapy. Due to their excellent penetration, quinolones have a theoretical advantage and several small studies have shown efficacy with these drugs over a 4-week course. Chronic carrier state is rare in children, but amoxicillin would be the drug of choice.

J All-India Ophthalmol Soc 18:135–137, 1970.

Miller SI, Hohmann EL, Pegues DA: Salmonella (including Salmonella typhi). In: Mandell GL, Bennett JE, Dolin R, eds: Principles and practice of infectious diseases. 4th edn. New York, Churchill Livingstone, 1995:2013–2033.

Parry CM, Hein TT, Dougan G, et al: Typhoid fever. N Engl J Med 347:1770–1782, 2002.

Rowe B, Ward LR, Threlfall EJ: Multidrug-resistant Salmonella typhi: a worldwide epidemic. Clinical Infectious Diseases 24(Suppl 1):S106– S109, 1997.

van Basten JP, Stockenbrugger R: Typhoid perforation: a review of the literature since 1960. Tropical and Geographical Medicine 46:336–339, 1994.

Surgical

●Prompt surgical intervention for severe intestinal bleeding or bowel perforation has been shown to reduce mortality substantially.

●There may be a role for cholecystectomy in management of the chronic carrier state if there is underlying biliary disease.

53 VARICELLA AND HERPES ZOSTER

052.9

Thomas J. Liesegang, MD

Jacksonville, Florida

COMPLICATIONS

In about 10% of patients, intestinal bleeding or perforation occurs, usually after the second week of illness. Bleeding occurs from ileal ulcers and may present as melena or bright red blood in stools. Perforation most often occurs unexpectedly after a few days of treatment when a patient has started to improve. Other unusual complications of typhoid fever include pneumonia, myocarditis, acute cholecystitis, hepatitis, nephritis, parotitis, orchitis, osteomyelitis and acute meningitis.

COMMENTS

Approximately 500 reported cases of typhoid fever occur each year in the United States. The percentage of these cases contracted abroad has increased to >70%, most of whom are children, adolescents or young adults. Most domestically acquired cases occur in outbreaks or among at-risk patients with underlying medical disease; the rate among patients with HIV is sixty times greater than the general population. Typhoid fever is a reportable disease in the United States.

Varicella

ETIOLOGY/INCIDENCE

Varicella-zoster virus causes two distinct syndromes. Primary infection presents as varicella (or chickenpox), a contagious and usually benign childhood illness that occurs in epidemics among susceptible children. The reactivation of the virus, usually associated with decline in cell-mediated immunity, occurs as herpes zoster (shingles). Varicella is spread through droplet infection with an initial viremia, and then viral spread to the skin and the eye. It is easily disseminated to susceptible individuals. Ninety-five percent of the population has serological evidence of prior VZV infection with or without symptomatic varicella. The incidence of varicella has diminished 70% after implementation of the varicella vaccine in 1995.

DIAGNOSIS

Varicella is an acute infectious exanthem characterized by fever, myalgias, anorexia, headache, sore throat, and vesicular eruptions on the skin. The disease is more severe in neonates,

TREATMENT

Systemic

This common, self-limiting disease requires minimal supportive therapy. Varicella in immunocompromised individuals may require aciclovir, famvir, or valaciclovir. These antivirals shorten the duration of illness; however, it is unclear whether the medication cost justifies use in otherwise healthy children. Zoster immune globulin can induce passive immunity within 96 hours of exposure in susceptible individuals at risk for severe infection. Systemic steroids are usually not indicated or are frequently contraindicated.

OCULAR COMPLICATIONS AND

TREATMENT

Varicella may be accompanied by a temporary conjunctivitis and episcleritis, which require no specific treatment. Rarely, microdendritic keratitis, nummular keratitis, disciform keratitis, mucous plaque keratitis, sclerokeratitis, and iritis may occur which require topical steroid treatment.

Herpes zoster

ETIOLOGY/INCIDENCE

The second clinical entity of VZV, herpes zoster disease, occurs from reactivation of VZV after initial establishment of latency within cells of the dorsal root ganglia throughout the body. Herpes zoster occurs in about 500,000 individuals annually in the US. Declining virus-specific cell-mediated immune responses, which occur naturally as a result of aging or are induced by immunosuppression, increase the frequency and severity of shingles. In patients with AIDS the incidence is 15 times greater than a non-AIDS population. In Africa HZ is especially common and severe.

DIAGNOSIS

Herpes zoster is an acute painful, vesicular eruption within a dermatomal distribution. Herpes zoster ophthalmicus (HZO), which defines the involvement of the ophthalmic division of the fifth cranial nerve, comprises about 20% of cases, and the eye is involved in 50% of these cases. The prodromal period before skin eruptions may feature fever, malaise, headache, and pain in the eye. The rash is initially erythematous, and then macules, papules, vesicles, pustules, and crusts develop. If the rash involves the nasociliary nerve distribution, there is a high rate of ocular complications.

COMPLICATIONS OF HZO

The ocular complications may vary markedly in severity and are complicated by contributing factors associated with the infection, with the inflammatory and immune changes (espe-

Eyelid

Rash, edema, ptosis, and late scarring with the development of entropion, ectropion, notch defects, or full-thickness lid loss.

Episclera/sclera

Affected during the acute stages of HZO or months later. Scleritis and episcleritis may persist for months. Scleritis has a tendency to progress toward limbal vasculitis and a sclerokeratitis. Posterior scleritis may result from an infiltrative perivasculitis and perineuritis.

Conjunctiva

Changes may include a papillary or follicular reaction, chronic hyperemia, and/or pseudomembrane formation with resultant conjunctival scarring.

Cornea

There is a wide range of complications:

●Pseudo dendrites and punctate epithelial keratitis: transient and rarely give rise to chronic keratitis;

●Nummular anterior stromal keratitis: resolves within the first month. Rarely becomes chronic and gives rise to lipid keratopathy and facet formation;

●Keratouveitis/endotheliitis with localized stromal edema: may represent direct viral infection of the endothelium or an immune reaction. Associated with uveitis, glaucoma, and iris atrophy;

●Disciform keratitis with deep disc-shaped area of stromal edema: may represent a VZV infection of the endothelium to an immune reaction. Resolves within a few months or may become chronic with a lipid keratopathy;

●Corneal mucous plaques: occur several months after HZO in a quiescent eye. They are variable in size, migratory in nature, and transitory around the cornea. May be immune related or represent chronic viral infection;

●Interstitial keratitis/lipid keratopathy: long-term corneal inflammation usually results in extensive corneal vascularization;

●Neurotrophic keratopathy: diminution of corneal sensation with subsequent a loss of epithelial integrity. May occur abruptly months following HZO with diffuse epitheliopathy, and chronic surface problems with calcareous plaque formation. It may progress to perforation or severe scarring;

●Corneal edema: temporary or permanent even in the absence of scarring and vascularization and is probably related to endothelial destruction by VZV;

●Exposure keratopathy: associated with a cicatricial eyelid changes leading to corneal desiccation.

Eye muscles

External ocular motor palsies with transient diplopia and involvement of the third, fourth, or sixth nerve may develop in 20%.

Retina and optic nerve

Rare complications include retinal perivasculitis, acute retinal necrosis, progressive outer retinal necrosis or ischemic optic neuritis.

Neurological

Acute neuralgia, post herpetic neuralgia (PHN), contralateral hemiplegia, encephalitis, or myelitis. The incidence and the duration of post herpetic neuralgia are correlated with age (about 7% of patients).

TREATMENT

Systemic

A course of systemic antiviral agents (aciclovir, valaciclovir, or famvir) is advised for all patients with defects of cell-mediated immunity. Controversy lingers regarding the use of antivirals for localized zoster in the normal host although they are recommended for all patients with HZO. Although any of the 3 systemic antivirals may lessen the complications of ocular zoster, there does not appear to be convincing or consistent evidence of the benefit of the systemic antivirals in preventing or treating the most severe complications of HZO. The drugs should be administered within 72 hours of the onset of the rash. Patients receiving combined corticosteroids and antivirals have an acceleration in cutaneous healing rates and a better quality of life, decreased use of analgesics, a decrease in the time to uninterrupted sleep, and a decrease in time to resumption of normal activities of daily living compared to those with antiviral alone. Steroids should not be used in those with depressed cell-medi- ated immunity. Aciclovir-resistant VZV have been reported in patients with advanced AIDS, requiring therapy with alternative drugs (e.g. foscarnet). There is no role for topical antiviral drugs in the management of herpes zoster.

Most treatment plans for PHN have anecdotal reports rather than controlled trials, so effectiveness is both complex and difficult to evaluate. Early antiviral appears to modify later PHN only marginally. For persistent cases, management in conjunction with a pain expert and a multifaceted approach is recommended. A variety of pharmacologic therapies exist for those who are not helped by mild analgesia. Clinical trials have shown that opioids, tricyclic antidepressants, and gabapentin reduce the severity or duration of post herpetic neuralgia, either as single agents or in combination.

Ocular

Topical steroids are recommended for chronic episcleritis and keratitis and for all cases of iritis. Careful monitoring of the use of topical steroids with very slow reduction and withdrawal prevents rebound effects and detects steroid responders.

Complications from severe neurotrophic keratopathy or exposure keratitis can require surgical intervention such as a partial tarsorrhaphy. Occasionally corneal surgery may be required in cases of perforation from neurotrophic corneas. Following a penetrating keratoplasty, HZO patients require close monitoring and therapy with lubrication and possibly lateral tarsorrhaphies. Cataract and glaucoma operations are generally uncomplicated, but topical steroids must be used postoperatively. Systemic steroids are indicated for markedly hemorrhagic rashes, proptosis with external ophthalmoplegia, optic neuritis and contralateral hemiplegia.

varicella as well as an increase in the incidence of herpes zoster. About 3% of childhood and 30% of adult vaccinees will have a breakthrough infection, but is usually much less severe than primary varicella. Epidemiologists predict that the more effective vaccination is at preventing varicella, the larger the future increase in zoster incidence. A vaccine trial is currently underway to assess whether varicella immunization of children affects the incidence of herpes zoster later in life. A separate trial is investigating whether periodic vaccination can prevent herpes zoster in the elderly.

REFERENCES

Liesegang TJ: Varicella-zoster virus eye disease. Cornea 18:511–531, 1999.

Severson EA, Baratz KH, Hodge DO, Burke JP: Herpes zoster ophthalmicus in Olmsted County, Minnesota: have systemic antivirals made a difference? Arch Ophthalmol 121:386–390, 2003.

Starr CE, Pavan-Langston D: Varicella-zoster disease: mechanisms of pathogenesis and corneal disease. Ophthalmol Clin N Amer 15:7–15, 2002.

Vafai A, Berger M: Zoster in patients infected with HIV: a review. Am J Med Sci 321:372–380, 2001.

Vazquez M: Varicella zoster virus infections in children after the introduction of live attenuated varicella vaccine. Curr Opin Pediatr 16:80–84, 2004.

Vrabec TR: Posterior segment manifestations of HIV/AIDS. Surv Ophthalmol 49:131–157, 2004.

54 YERSINIOSIS 020.9

K. Matti Saari, MD, MedScD, FEBO

Turku, Finland

ETIOLOGY/INCIDENCE

Yersiniosis is caused by infection with one of the invasive rod-shaped Yersinia bacteria; these organisms are small, nonmotile, gram-negative coccobacilli. The two species that cause disease in humans are Y. enterocolitica and Y. pseudotuberculosis; they are closely related to the bubonic plague bacillus

Y.pestis.

Y. enterocolitica serotypes 3, 4, 5, 8, and 9 and Y. pseudotuberculosis are the principal causes of yersiniosis; the yersinioses are distributed worldwide. The bacilli have been isolated from a wide variety of domestic and wild animals, and although the mode of transmission of Yersinia spp. is not fully certain, the primary mode appears to be through the ingestion of fecally contaminated water or food. Transmission to humans through contact with infected animals, especially swine, and from person to person can occur in rare instances.

The incubation period is 4 to 10 days.

toms, such as acute terminal ileitis or mesenteric adenitis.

●Adults may present with enteritis, including diarrhea, nonspecific abdominal pain, nausea, vomiting and fever.

●In young and middle-aged adults with HLA-B27 antigen, nonpurulent reactive arthritis, often with myalgia and sacroiliitis, is more common.

●In women of later middle age, erythema nodosum is a frequent symptom.

Less common symptoms of yersiniosis include the following:

●Carditis;

●Septicemia;

●Glomerulonephritis;

●Hepatitis;

●Hemolytic anemia.

Although septicemia with serious complications may occur in debilitated and elderly patients, the prognosis for Yersinia infections is generally good, especially if diagnosed early and treated promptly.

In children, the diarrhea associated with Y. enterocolitica often is self-limited, and the role of antibiotic therapy is unclear; subacute localizing forms of infection sometimes occur with Y. pseudotuberculosis, particularly in patients with concurrent underlying disease.

resolve completely, but in 30% to 50% of cases, the uveitis may recur after a lapse of 1 month to 3 years.

Reactive conjunctivitis may occur in one or both eyes from 4 to 17 days after the onset of Yersinia infection; conjunctival symptoms are mostly mild, although the patient may complain of ocular redness and a burning sensation. More rarely, slight ocular pain, palpebral edema, and purulent exudate may be found.

Reactive conjunctivitis resolves spontaneously in 7 days.

Laboratory findings

Because yersiniosis may present with such a wide spectrum of symptoms, diagnosis may easily be missed. This infection should always be considered in patients with fever and abdominal symptoms of unknown origin after appendicitis has been ruled out.

When a diagnosis of yersiniosis is suspected, cultures should be made of:

●Stool samples;

●Conjunctival discharges.

A presumptive diagnosis can be made from serologic test results on the demonstration of:

●Enzyme-linked immunosorbent assay for detection of IgA and IgM antibodies to Yersinia spp. showing elevated antibody levels, indicating a recent infection;

●An elevated erythrocyte sedimentation rate, characteristic for yersiniosis in patients of all ages.

Ocular

Pyogenic intraocular involvement (microbial invasion of the eye) is very rare in patients with yersiniosis, but the following have been reported:

●Parinaud’s oculoglandular syndrome with:

●Corneal perforation; and

●Panophthalmitis;

●Leading to visual loss.

Reactive ocular inflammation is occasionally associated with patients with HLA-B27 antigen; the causative agent cannot be isolated from the eye. Symptoms in these patients include:

●Acute anterior uveitis;

●Conjunctivitis;

●Reiter’s syndrome.

Reactive acute anterior uveitis may follow from 5 days to 1 month after the onset of Yersinia infection, with the following consistent signs:

●Conjunctival redness;

●Photophobia;

●Ocular pain;

●Decreased vision;

●Increased lacrimation;

●Pericorneal ciliary injection;

●Aqueous cells and flare;

●Fine keratic precipitates.

Other signs and symptoms of Yersinia can include the following:

●Vasodilation of iris vessels;

●Fibrinous exudation in the aqueous humor;

●Cells in the vitreous humor;

●Macular edema.

Patients with reactive ocular inflammation after Yersinia infection are HLA-B27 positive.

TREATMENT

Systemic

Most Y. enterocolitica strains are sensitive to:

●Ceftazidime;

●Chloramphenicol;

●Ciprofloxacin;

●Gentamicin;

●Tetracycline;

●Tobramycin;

●Trimethoprim-sulfamethoxazole.

However, success with these drugs is not uniform, and Yersinia spp. have been found to be resistant to amoxicillin, ampicillin, carbenicillin, cephalosporin, and penicillin.

Drug therapy must be started promptly when Yersinia infection is suspected; the usual drugs of choice are:

●Tetracycline 250 to 500 mg PO every 6 hours for 10 days;

Alternatives are:

●Sulfamethoxazole 800 mg and trimethoprim 160 mg PO b.i.d. or t.i.d.;

●Gentamicin 0.8 mg/kg IM initially followed by 0.4 mg/kg IM every 6 hours.

Therapy should be continued for at least 24 to 48 hours after the fever and other symptoms have subsided.

istered hourly for 8 days and then tapered to 1 drop every 6 hours until the infection is resolved.

With corneal involvement:

●Gentamicin 20 to 40 mg/day by sub-Tenon’s injection for 4 to 5 days should be given; this series may be followed by two additional injections on alternate days;

●Topical atropine solution 1% 1 drop every 6 hours may be used for uveitis;

●Scopolamine 0.25% 1 drop every 6 hours may be substituted for patients sensitive to atropine.

Reactive conjunctivitis associated with Yersinia infection usually resolves in 1 week without treatment.

Reactive iritis should be treated with topical corticosteroids such as:

●Dexamethasone 0.1%;

●Prednisolone 0.5% or 1%.

Either of these drugs should be administered as eyedrops every hour while awake and in an equivalent concentration in ointment form at night, plus:

●Scopolamine 0.25% drops t.i.d.

In patients with reactive ocular inflammation associated with yersiniosis, antibiotic therapy should be administered only in cases in which high levels of IgM antibodies indicate recent infection, when Yersinia organisms can be cultured from stool samples, or when diarrhea, abdominal pain, or both are still present or closely connected with the illness.

In cases with fulminant onset of reactive ocular inflammation, systemic corticosteroids such as:

●Prednisolone 40 to 60 mg/day PO may be used; the dose should be tapered as soon as the inflammation has subsided.

The management of Y. enterocolitica endophthalmitis or panophthalmitis is extremely difficult, and usually eyesight is lost at this stage of the disease.

colitis, superinfections, and photosensitivity. Patients taking tetracyclines should not sunbathe. Products containing aluminum, magnesium, or calcium ions (antacids, milk, and milk products) decrease the absorption of tetracyclines and should not be taken during the hour before or 2 hours after an oral dose of tetracycline. Tetracyclines should be avoided during pregnancy and in children younger than 8 years because of irreversible deposition of the substance in growing bones and teeth.

Gentamicin must be used with caution in patients who have renal impairment; both nephrotoxicity and neurotoxicity with involvement of the eighth cranial nerve have been reported with the use of gentamicin.

Chloramphenicol may have severe side effects, although they are rather uncommon. Adverse effects reported with this drug include skin rashes, fever, gastrointestinal disturbance, bone marrow depression, and the gray-baby syndrome.

COMMENTS

Pyogenic ocular involvement in patients with Yersinia infection is very uncommon but may cause Parinaud’s oculoglandular syndrome with hyperemia, edema, necrosis, and ulcer of the conjunctiva; clouding, ulcer, and perforation of the cornea; hypopyon and cataract; vascular constriction and hemorrhages of the retina; and endophthalmitis or panophthalmitis and visual loss. Pyogenic ocular manifestations in patients with yersiniosis should be treated aggressively with systemic and local antibiotics and with emergency pars plana vitrectomy if necessary.

Reactive ocular inflammation after Yersinia infection provides the best example of an association among acute anterior uveitis or reactive conjunctivitis, HLA-B27, and an identified infectious agent. Acute anterior uveitis is typically unilateral and resolves during corticosteroid therapy, on average during the first 6 weeks. Reactive conjunctivitis is generally mild and resolves in 1 week without any treatment. Reactive ocular inflammation associated with Yersinia infection often occurs with reactive arthritis, myalgia, and sacroiliitis.

Surgical

In cases of Yersinia endophthalmitis or infectious keratitis, surgery may become necessary in an effort to salvage the eyes. If corneal perforation occurs:

●A corneal patch graft may be indicated to seal the perforation;

●Emergency pars plana vitrectomy may be indicated.

Vitrectomy is performed to remove infectious organisms, to confirm their identity and antibiotic sensitivity by vitreous culture, and to enable the:

●Intravitreal injection of ceftazidime 2.25 mg in 0.1 mL of isotonic saline.

The postoperative therapeutic regimen should include systemic antibiotics, daily sub-Tenon’s injections of 20 to 40 mg of either gentamicin or tobramycin, or of 100 mg of ceftazidime, and the topical instillation of 14 mg/mL fortified gentamicin or 11 mg/ mL fortified tobramycin every 30 minutes for the first few days, which can then be tapered as indicated.

REFERENCES

Cancino-Diaz JC, Vargas-Rodriguez L, Grinberg-Zylberbaum N, et al: High levels of IgG class antibodies to recombinant HSP60 kDa of Yersinia enterocolitica in sera of patients with uveitis. Br J Ophthalmol 88:247– 250, 2004.

Chin GN, Noble RC: Ocular involvement in Yersinia enterocolitica infection presenting as Parinaud’s oculoglandular syndrome. Am J Ophthalmol 83:19–23, 1977.

Mattila L, Granfors K, Toivanen A: Acute anterior uveitis after yersinia infection. Br J Ophthalmol 66:209–212, 1982.

Saari KM: The eye and reactive arthritis. In: Toivanen A, Toivanen P, eds: Reactive arthritis. Boca Raton, CRC, 1988:113–124.

Saari KM, Laitinen O, Lierisalo M, et al: Ocular inflammation associated with Yersinia infection. Am J Ophthalmol 89:84–95, 1980.

Saari KM, Maki M, Paivonsalo T, et al: Acute anterior uveitis and conjunctivitis following yersinia infection in children. Int Ophthalmol 9:237– 241, 1986.