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DIAGNOSTIC TEST FOR HERPES (PEMPHIGOID) GESTATIONIS, AN

IMMUNOBULLOUS DISEASE OF PREGNANCY AND THE PUERPERIUM

Introduction

Herpes gestationis, also known as pemphigoid gestationis,

is a rare disease of pregnancy and the puerperium. It is

characterized by tense blisters on skin with prominent itching.

Herpes gestationis may develop anytime during pregnancy

or within a few weeks of delivery, but typically occurs in the

second to third trimester and resolves within several weeks of

delivery. Recurrences in subsequent pregnancies may be earlier

and with greater severity. Recurrences may also occur with

menstrual cycles and with hormonal treatment.

Urticarial papules and plaques develop into vesiclesand bullae initially around the umbilicus and spreading in a

generalized distribution often involving palms and soles but

usually sparing mucosa. Blistering occurs in a subepidermal

location, and complement-fixing IgG antibodies to basement

membrane zone components are present in patients sera. In

most patients, IgG1 and IgG3 autoantibodies are directed to

the membrane-proximal NC16A domain of the 180-kd bullous

pemphigoid (BP) antigen (BP180). Like in pemphigoid,

blistering likely occurs when IgG antibodies bind to

hemidesmosomal proteins in the basement membrane zone and

activate complement. Inflammatory cells including eosinophils

are attracted to the area. Once there, the inflammatory cells

release proteases and other mediators that degrade the cell

adhesiveness of hemidesmosomes and cause dermal-epidermal

separation. Complement is found at the basement membrane

zone in perilesional tissue, and complement-fixing IgG basementmembrane zone antibodies are present in greater than 50 percent

of patients sera with localization on the epidermal side of

split skin. Diagnosis of herpes gestationis is aided by serum

studies to detect such antibodies, which are referred to as herpes

gestationis factor.

ARUP Laboratories

500 Chipeta Way

Salt Lake City, UT 84108

(800) 242-2787

(801) 583-2787

Reorder Number: 1500.04

www.aruplab.com

November 2004

Complement-fixing antibodies to human skin substrate

are detected by incubating dilutions of patient serum and fresh

human complement (serum obtained from a normal individual

and used within two hours) with human epidermis split at the

basement membrane zone in an indirect immunofluorescence

assay (IFA). Serial twofold dilutions of serum and fresh

complement are incubated with human skin substrate split at the

basement membrane zone followed by fluoresceinated antibodyto human C3. When positive, the pattern of staining on human

skin split is recorded and limiting dilutions are carried out for

endpoint titers to establish levels of circulating antibodies.

Clinical Significance

Methodology

Herpes Gestationis Factor

Testing for herpes gestationis factor is appropriate for

patients suspected of having herpes (pemphigoid) gestationis.

An important consideration is the clinical variability with

which immune-mediated skin diseases present. For example,

herpes gestationis may have an urticarial phase before blistering

develops, and immunobullous diseases may resemble common

dermatoses, including other pruritic dermatoses of pregnancy,

potentially causing delay in diagnosis and treatment if not tested

appropriately. Herpes gestationis factor testing by IFA is a well

established test and should be performed when the diagnosis

herpes gestationis is considered. Practitioners should consider

evaluating for IgG and IgA basement membrane zone antibodies

(test numbers 0092056 and 0092057) when initially performingthis test.

Appropriate Use of Test

Complement-fixing IgG basement membrane zone

antibodies (herpes gestationis factor) present in titers greater

than 1:10 showing an epidermal (roof of skin separation)

pattern of antibody staining on split human skin are positive

Complement-fixing basement membrane zone antibodies

by IFA are negative ( less than or equal to 1:10) in normal

individuals.

Laboratory Diagnosis

Features and Benefits

Diagnostic test for herpes gestationis.

Helpful in distinguishing pruritic dermatoses of pregnancy.Specific and sensitive IFA testing method.

Clients can order this test alone or with other

immunobullous disease testing.

FOR TECHNICAL

INFORMATION,

CONTACT:

FOR SCIENTIFIC

AND CLINICAL

INFORMATION,

CONTACT:

Marjorie Campbell, B.S.

Technical Supervisor,

Immunodermatology Lab

(801) 581-7139toll free (866) 266-5699

Ellen Hardy,

Laboratory Coordinator,

Immunodermatology Lab(801) 581-7139 or 6465

toll free (866) 266-5699

fax (801) 581-6484

Kristin M. Leiferman, M.D.Co-Director,

Immunodermatology Lab

(801) 581-6465

(801) 339-3191 (pager)

John J. Zone, M.D.

Co-Director,

Immunodermatology Lab

(801) 581-6465

(801) 581-5516

WEB ADDRESS:http://uuhsc.utah.edu/derm/

immunoderm/

Diagnosis of herpes gestationis is aided by specific

immunodermatologic testing to detect circulating herpes

gestationis factor. Testing for these complement-fixing IgG

basement membrane zone antibodies is highly sensitive

and specific for herpes gestationis and also is important in

distinguishing herpes gestationis from other immunobullous

diseases, including dermatitis herpetiformis, bullous

pemphigoid, and pemphigus. Prompt, accurate diagnosis is

essential for planning therapy to minimize morbidity and patient

discomfort.

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0092283 Herpes Gestationis Factor HG FACTOR

(IgG Complement-Fixing Basement Membrane Zone Antibodies)

Please view the ARUP Users Guide for additional test information.

References

Borrego L, et al. Polymorphic

eruption of pregnancy

and herpes gestationis:

comparison of granulatedcell proteins in tissue and

serum. Clin Exp Dermatol

1999; 24:213-225.

Harman KE. New laboratory

techniques for the

assessment of acquiredimmunobullous disorders.

Clin Exp Dermatol 2002;27:40-46.

Lin MS, et al. Molecular

mapping of the majorepitopes of BP180

recognized by herpes

gestationis autoantibodies.

Clin Immunol 1999;

92:285-292.

Matsumura K, et al.The majority of bullous

pemphigoid and herpes

gestationis serum samples

react with the NC16A

domain of the 180-kDa

bullous pemphigoid antigen.

Arch Dermatol Res 1996;

288:507-509.Mutasim DF, Adams BB.

Immunofluorescence in

dermatology. J Am Acad

Dermatol 2001; 45:803-822.

Shornick JK. Herpes

gestationis. Dermatol Clin

1993; 11:527-533.

Test Information

MEDICARE COVERAGE OF LABORATORY TESTING

Please remember when ordering laboratory tests that are billed to Medicare/Medicaid, or other federally-funded programs, the following requirements apply:

Only tests that are medically necessary for the diagnosis or treatment of the patient should be ordered. Medicare does not pay for screening tests, except for

certain specifically approved procedures, and may not pay for non-FDA approved tests or for those tests considered experimental.

If there is reason to believe that Medicare will not pay for a test, the patient should be informed. The patient should then sign an Advance Beneficiary Notice

(ABN) to indicate that he or she is responsible for the cost of the test if Medicare denies payment.Effective January 1, 1998, the ordering physician must provide an ICD-9 diagnosis code or narrative description, if required by the local fiscal intermediary

or carrier.

Organ- or disease-related panels should be billed only when all components of the panel are medically necessary.

Both ARUP- and client-customized panels should be billed to Medicare only when every component of the customized panel is medically necessary.

Medicare National Limitation Amounts for CPT codes are available through CMS or its intermediaries. Medicaid reimbursement will be equal or less than the

amount of Medicare reimbursement.

The CPT codes for the tests profiled in this technical bulletin are in the Test Information section. The codes reflect ARUPs interpretation of CPT coding require-

ments, based upon AMA guidelines. CPT codes are provided only as guidance to assist you in billing. ARUP strongly recommends that clients reconfirm CPT code

information with their local intermediary or carrier. CPT coding is the sole responsibility of the billing party. Also, if you have further questions regarding the ap-

propriate use of any test, please contact ARUPs Client Services department.

The regulations described above are only guidelines. Additional procedures may be required by your local intermediary or carrier.

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ARUP Laboratories, November 2004

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