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edema, and pelvic or thigh pain.

PATIENT EDUCATION

ACOG at http://www.acog.org, the Society of Gynecologic Oncology at http://www.sgo.org, the Foundation for Women’s Cancer at http://www.foundationforwomenscancer.org

American Cancer Society at http://www.cancer.org, and the National Cancer Institute at http://www.cancer.gov

PROGNOSIS

If detected early, invasive cervical cancer can be treated successfully; 5-year survival for women with cancer in the earliest stage (stage 1A, in which the cancer has minimal spread to the inside of the cervix) is estimated at 92%.

An elevated squamous cell carcinoma antigen (SCC-Ag) serum levels estimated by ELISAtechnique can be used to predict the clinical response to neoadjuvant chemotherapy and residual disease; persistently elevated SCCAg level at 2 to 3 months after RT had a significantly higher incidence of treatment failure

Serum SCC-Ag levels are useful for monitoring treatment efficacy, disease progression, and recurrence. In general, increased serum SCC-Ag levels reflect disease progression and poor prognosis in SCCs. Thus, the combination of clinical pelvic examination and SCC-Ag levels provides useful information for the further need of treatment.

COMPLICATIONS

Loss of ovarian function from radiotherapy or indication for bilateral oophorectomy

Hemorrhage

Pelvic infection

Genitourinary fistula

Bladder dysfunction

Sexual dysfunction

Ureteral obstruction with renal failure

Bowel obstruction

Pulmonary embolism

Lower extremity lymphedema

REFERENCES

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1.Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin

Number 131: screening for cervical cancer. Obstet Gynecol. 2012;120(5):1222–1238.

2.International Federation of Gynecology and Obstetrics. Global guidance for cervical cancer prevention and control. http://www.rho.org/files/FIGO_cervical_cancer_guidelines_2009.pdf. Accessed January 4, 2018.

3.Rydzewska L, Tierney J, Vale CL, et al. Neoadjuvant chemotherapy plus surgery versus surgery for cervical cancer. Cochrane Database Syst Rev. 2012;(12):CD007406.

4.Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017;390(10103):1654–1663.

ADDITIONALREADING

American Society for Colposcopy and Cervical Pathology. Updated consensus guidelines for managing abnormal cervical cancer screening tests and cancer precursors. http://www.asccp.org/Portals/9/docs/ASCCP%20Management%20Guidelines_ Accessed January 12, 2017.

Martin-Hirsch PP, Paraskevaidis E, Bryant A, et al. Surgery for cervical intraepithelial neoplasia. Cochrane Database Syst Rev. 2013;(12):CD001318.

National Comprehensive Cancer Network. NCCN Guidelines: cervical cancer. http://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. Accessed January 4, 2017.

Scarinci IC, Garcia FA, Kobetz E, et al. Cervical cancer prevention: new tools and old barriers. Cancer. 2010;116(11):2531–2542.

SEE ALSO

Abnormal Pap and Cervical Dysplasia

CODES

ICD10

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C53.9 Malignant neoplasm of cervix uteri, unspecified

C53.0 Malignant neoplasm of endocervix

C53.1 Malignant neoplasm of exocervix

CLINICALPEARLS

Cervical cancer is the second most common malignancy in women worldwide. Improving access to screening is likely to have the greatest impact in reduction of the burden of disease.

Women with cervical cancer may be asymptomatic and have a normal physical exam.

Surgical management is an option for patients with early-stage tumors. Chemoradiation is the first-line therapy for higher stage tumors.

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CHICKENPOX (VARICELLAZOSTER)

Kay A. Bauman, MD, MPH

BASICS

DESCRIPTION

Common, highly contagious generalized exanthem characterized by crops of pruritic vesicles on the skin and mucous membranes following exposure to varicella-zoster virus (VZV)

VZV is spread by respiratory (airborne) droplets and direct contact with vesicles.

VZV establishes latency in the dorsal root ganglia; reactivation results in zoster (shingles).

Outbreaks tend to occur late winter through early spring in temperate climates.

Usual incubation period is 14 to 16 days (range: 10 to 21). Patients are infectious from ~48 hours before appearance of vesicles until the final lesions have crusted. Historically, most people acquired chickenpox during childhood and develop lifelong immunity. Varicella is part of recommended primary vaccination schedule.

System(s) affected: nervous, skin/exocrine

Synonym(s): varicella

EPIDEMIOLOGY

Predominant age: peak incidence 3 to 9 years but may occur at any age

Predominant gender: male = female

Incidence

Decreasing incidence since routine vaccination; estimated 3.5 million cases annually prior to vaccine, with an incidence of 8–9% in children age 1 to 9 years

Reported U.S. varicella cases: 1991, 147,076; 2015, 9,789 cases (1,2)

Prior to vaccine, ~100 deaths/year were reported in the United States; in 2015, there were six reported deaths (2).

U.S. rates: 1994, prior to vaccine: 136/100,000 persons; 2013 to 2014: <0.001/100,000 persons

Rates of varicella in the United States dropped after vaccine introduction until

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mid-2000s when they plateaued; second dose of vaccine recommended in

2006, and rates have again declined

In developing countries, varicella is still associated with a severe disease burden.

Susceptible (immunologically naive) individuals exposed to varicella are at risk to develop disease and are also potentially infectious for 21 days.

ETIOLOGYAND PATHOPHYSIOLOGY

Skin lesions are histologically identical to herpes simplex virus.

In fatal cases, intranuclear inclusions are found in vascular endothelium and most organs.

VZV is a double-stranded DNAvirus of the α-Herpesviridae subfamily.

Humans are primary disease reservoir.

RISK FACTORS

No history of prior varicella infection or immunization

Immunocompromised (especially children with leukemia/lymphoma in remission or receiving high-dose corticosteroids)

Pregnancy

Geriatric Considerations

Infection is more severe in adults.

Reactivation of latent infection causes zoster (shingles).

Herpes zoster vaccine, a live attenuated vaccine, is recommended as a single dose for all persons ≥60 years regardless of prior clinical history of shingles or chickenpox. The vaccine reduces shingles by 51% and the incidence of painful postherpetic neuralgia by 67%.

The vaccine can be administered to persons ≥60 years who are receiving therapy to induce low-level immunosuppression but should not be given to highly immunocompromised patients. Giving the vaccine prior to starting chemotherapy significantly lowers risk of zoster (http://www.cdc.gov/vaccines/vpd-vac/shingles/hcp-vaccination.htm).

Although approved by the FDAfor patients 50 to 59 years of age, the vaccine is not routinely recommended in this age group.

Primary viral pneumonia is the most common cause of death from varicella.

Pediatric Considerations

Neonates born to mothers who develop chickenpox from 5 days before to 2

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days after delivery are at risk for serious disease and should receive varicellazoster immune globulin (VZIG).

Newborns are at highest risk for severe disease during the 1st month of life, especially if mother is seronegative.

Delivery prior to 28 weeks increases risk.

Varicella bullosa is seen mainly in children <2 years. Lesions appear as bullae instead of vesicles. The clinical course is otherwise similar.

Septic complications and encephalitis are the most common causes of death from zoster in children.

Avoid aspirin/acetylsalicylic acid in children because of link to Reye syndrome.

Pregnancy Considerations

25% risk of transplacental infection after maternal infection

Congenital malformations are seen in 2% of patients when the fetus is infected during the 1st or 2nd trimesters, characterized by limb atrophy, cutaneous scarring, and occasional CNS and eye manifestations.

Morbidity (e.g., pneumonia) is increased in women infected during pregnancy.

GENERALPREVENTION

Isolate hospitalized patients.

When indicated, administer passive immunization using VZIG within 96 hours (can be as long as up to 10 days) after exposure. VZIG recommended for:

–Patients exposed to chickenpox or shingles who are immunocompromised, newborns of mothers with onset of chickenpox <5 days before delivery or <2 days after delivery, premature infants (<28 weeks) exposed in neonatal period either whose mothers are not immune, or babies who weigh <1,000 g

regardless of maternal immunity

Active immunization prevents or reduces the severity of varicella if given within 72 hours of exposure.

Active immunization: varicella virus vaccine (Varivax): live attenuated vaccine recommended by ACIPfor immunization of healthy patients ≥12 months who have not had chickenpox

–12 months to 12 years: initial dose 0.5 mLSC at age 12 to 15 months; second dose at age 4 to 6 years. Single dose is 85–94% effective in preventing severe disease. The 2-dose regimen is 96–98% effective. Breakthrough disease generally has <50 lesions, shorter duration, and lower fever incidence (3)[A].

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–≥13 years: two 0.5 mL SC doses 4 to 8 weeks apart, seroconversion rates

78–82% after 1 dose, 99% after 2 doses; adult efficacy in lower end of this range

–2014 U.S. estimate: 91% one or more-dose vaccine coverage for children 19 to 35 months (4)

–Vaccine side effects are pain and redness at the vaccine site (19% of children; 24% of teens and adults). 1 in 10 develops fever. 1 in 25 will develop a mild varicella-like rash up to 1 month after vaccination.

–Vaccine contraindications

Severe allergic reaction (e.g., anaphylaxis) to a previous dose or vaccine component

Severe immunodeficiency (e.g., HIV patients with very low CD4 counts, chemotherapy, congenital immunodeficiency, long-term immunosuppressive therapy)

Pregnancy

MMRV vaccine, combines the measles, mumps, and rubella vaccine with varicella, is equally effective. There are rare reports of an increased risk of febrile seizures 5 to 12 days after vaccination in 1/2,300 to 2,600 patients.

May be considered for a subset of HIV-positive children in CDC class I with CD4 >25%

–Vaccine recipients who develop a rash should avoid contact with immunocompromised people, pregnant women who have never had chickenpox, and their newborns.

–Allow at least 3 months between doses 1 and 2 in children needing catch-up vaccination.

DIAGNOSIS

HISTORY

Prodromal symptoms: fever, malaise, anorexia, mild headache

Malaise, muscle aches, arthralgias, and headache are more common in adults.

Subclinical in ~4% of cases

Characteristic rash

PHYSICALEXAM

Characteristic rash: crops of vesicles on erythematous bases (“dew drops on a rose petal”)

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Lesions erupt in successive crops.

Progress from macule to papule to vesicle, then begin to crust

Pruritic rash is present in various stages of development.

Lesions may be present on mucous membranes, both oral and vaginal.

DIFFERENTIALDIAGNOSIS

Herpes simplex: herpes zoster

Smallpox

Impetigo

Coxsackievirus infection

Scabies

Dermatitis herpetiformis

Drug rash

Rickettsial pox infection

DIAGNOSTIC TESTS & INTERPRETATION

The diagnosis of chickenpox is primarily clinical; testing generally for complicated cases or epidemiologic studies.

Initial Tests (lab, imaging)

VZV polymerase chain reaction (PCR) is the current method of choice (best is fluid from intact vesicle).

Leukocyte count varies; marked leukocytosis suggests secondary infection.

Multinucleated giant cells on Tzanck smear from vesicle scrapings

Isolate virus from human tissue culture.

Follow-Up Tests & Special Considerations

Serologies show acute (IgM) or prior (IgG) infection.

Visualization by electron microscopy, tissue culture (costly), and various methods of acute and convalescent sera collection: latex agglutination (most available), enzyme immunoassay, indirect immunofluorescence antibody, fluorescent antibody to membrane assay, or PCR assay, which can detect wild from vaccine viral strains

Vaccine-modified cases can be more difficult to diagnose; PCR testing of skin lesions is most sensitive and specific for diagnosing varicella, especially in vaccinated persons.

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TREATMENT

Outpatient, except for complicated cases

GENERALMEASURES

Supportive/symptomatic treatment

Antihistamines and/or oatmeal baths for itch

Acetaminophen and/or ibuprofen for pain and fever

Clipping nails can help prevent scarring or secondary infection from excessive itching.

MEDICATION

First Line

Supportive: antipyretics for fever; avoid aspirin in children.

Local and/or systemic antipruritic agents for itching VZIG available for passive immunization for:

–Immunocompromised patients, newborn infants of mothers who have signs and symptoms of varicella at the time of delivery; premature infants born at 28 weeks or more whose mothers do not have evidence of immunity to varicella; premature infants <28 weeks’gestation or who weigh <1,000 g regardless of maternal immunity

–Give VZIG within 96 hours after exposure (5).

Acyclovir: decreases duration of fever and shortens time of viral shedding; recommended for adolescents, adults, and high-risk patients; most beneficial if initiated early in the disease (≤24 hours)

–2- to 16-year-old patients: 20 mg/kg/dose (max 800 mg/dose) QID for 5 days

–Adults: 800 mg 5 times daily for 5 days

Contraindication

– Hypersensitivity to the drug

Precautions

–Renal insufficiency with acyclovir

–Concurrent administration of probenecid increases half-life; increased effects with zidovudine (e.g., drowsiness, lethargy)

Second Line

Famciclovir: 500 mg TID for 7 to 10 days (adults)

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Valacyclovir: 1 g TID for 7 to 10 days (adults)

ONGOING CARE

FOLLOW-UPRECOMMENDATIONS

Patient Monitoring

Not needed in mild cases. Intensive supportive care may be required in the setting of complications.

Activity as tolerated. Children may return to school when lesions have completely scabbed.

DIET

No special diet

PATIENT EDUCATION

In otherwise healthy children, chickenpox is rarely serious and the recovery is almost always complete.

Native chickenpox typically confers lifelong immunity.

Asecond attack is rare, but subclinical infection can occur; this happens occasionally after vaccination in children.

Latent infection may recur years later as herpes zoster in adults (and sometimes in children).

Fatalities are rare.

COMPLICATIONS

Although only 2% of cases are reported after 2nd decade, 35% of deaths occur in this age group.

Secondary bacterial infection: cellulitis, abscess, erysipelas, sepsis, septic arthritis/osteomyelitis, or staphylococcal pyomyositis

Pneumonia: 20–30% of adults with chickenpox have lung involvement; 1/400 is hospitalized.

Encephalitis (the most common CNS complication)

Meningitis; Reye syndrome

Purpura, thrombocytopenia Glomerulonephritis; arthritis; hepatitis

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