Case Report

Oral pemphigus vulgaris occurring duringpregnancy

Joseph K. MuhammadMichael A. O. LewisSt. John Crean

Department of Oral Surgery, Medicine andPathology, University of Wales of Medicine,Cardiff, UK

Correspondence to:Michael A. O. LewisDepartment of Oral Surgery, Medicine andPathology, Dental School, University Of WalesCollege of Medicine, Heath Park, Cardiff, CF14 4XN,United Kingdom

Accepted for publication September 7, 2001

Copyright c Munksgaard 2002J Oral Pathol Med . ISSN 0904-2512

Printed in Denmark . All rights reserved

121

AbstractThere have been few reports describing the occurrence of pem-phigus vulgaris (PV) during pregnancy. The patient described inthis case report is interesting because the PV that developedduring her pregnancy was confined to her mouth. It has beensuggested that prompt treatment with systemic steroids pre-vents development of PV in cutaneous tissues. In this case,early control of the condition is believed to have eliminated theneed for high dose steroids throughout the remainder of thepregnancy. In addition, this therapeutic approach could havecontributed to the birth of a baby free of PV. Resolution of thepresenting oral symptoms allowed the mother to resume a nor-mal diet, allaying her anxiety about the possible effects of poornutritional intake on foetal development. Aspects of clinicalmanagement considered in this report include the choice ofimmunospuppressive therapy and the multidisciplinary care in-volving both dental and obstetric specialists.

Keywords: early treatment; multidisciplinary care; pemphigusvulgaris; pregnancy

J Oral Pathol Med 2002: 31: 121–4

A 28-year-old Caucasian female presented at the oral medicine clinic

on an emergency basis with a five-week history of oro-pharyngeal

ulceration, which was becoming increasingly painful and more

widespread. The case records revealed that the patient had been

seen eight months earlier complaining of pain from her gingivae

and palate. A routine mucosal biopsy demonstrated histophatholog-

ical features that were suggestive of either erythema multiforme or

pemphigus vulgaris. A clinical diagnosis of erythema multiforme

had been preferred due to the short duration of symptoms and the

young age of the patient. This clinical diagnosis was supported by

the total resolution of the original symptoms following a short

course of systemic steroids. The patient had subsequently not been

followed-up as she had remained free of symptoms and had there-

fore failed to attend for review.

At the time of eventual re-presentation the patient indicated that

Lewis et al.

she was 12 weeks pregnant and the ulceration had started 8 weeks

into the pregnancy. The pain associated with the oral symptoms

was limiting her ability to eat and she was becoming increasingly

worried that her poor intake of food was going to harm the develop-

ment of the foetus. The patient’s medical history failed to reveal

any significant illnesses or concomitant drug therapy. The patient

was a non-smoker and drank alcohol occasionally. The patient had

a child aged 10 years by a different partner. This first pregnancy

had been uneventful.

Extra-oral clinical examination was unremarkable. Intra-oral ex-

amination revealed extensive areas of erosion affecting the upper

labial mucosa (Fig. 1), lower labial mucosa (Fig. 2), soft palate, floor

of the mouth, gingivae and buccal mucosa. The level of oral hygiene

was poor and there was marked halitosis. A provisional diagnosis

of a vesicullo-bullous condition was made, with a differential diag-

nosis of erythema multiforme, mucous membrane pemphigoid and

Fig.1. Mucosal erosions affecting the upper anterior attached gingivae la-bial mucosa.

Fig.2. Extensive erosion of the lower labial mucosa.

122 J Oral Pathol Med 31: 121–4

pemphigus. There was no improvement in the symptoms despite

treatment with topical betamethasone, 0.5 mg tablet (Betnesol A,

Medeva, Leatherhead, UK) dissolved in water and used as a mouth-

wash for two minutes, three times daily. In addition, the patient

was provided with a beclomethasone inhaler (BecloforteA, Allen &

Hambury’s Ltd, Uxbridge, UK) and instructed to direct two puffs

(250 mg each) at the affected mucosa twice daily, if symptoms failed

to improve.

At review after a further five days, the lesions were failing to

resolve and a diagnosis of erythema multiforme was now thought

unlikely. A mucosal biopsy of a lesional area in the buccal sulcus

was obtained and the tissue was sent for both routine processing

and direct immunofluorescence. Histopathological examination of

a haematoxylin and eosin stained preparation showed suprabasal

clefting and acantholysis, features consistent with PV. Direct

immunofluorescence on fresh tissue was positive and revealed the

presence of IgG in the intercellular spaces throughout the epithel-

ium, a pattern of immunofluorescence consistent with a diagnosis

of PV.

It was now evident that the patient required systemic steroid

therapy. However, in view of the pregnancy, further management of

the patient was discussed with her obstetrician, before a decision

was made to prescribe prednisolone 20 mg orally once per day. It

was felt that hospital admission at this stage was not required. At

review one week later, the oral lesions had improved considerably

and the pain reduction had enabled the patient to return to a normal

diet. Over the next three weeks, the dose of prednisolone was gradu-

ally reduced in 5 mg increments per week to a level of 5 mg once a

day. This low level of prednisolone was continued for the duration

of the pregnancy without any recurrence of the oral lesions. The

pregnancy and the delivery were uneventful and a healthy boy,

weighing 10lb 2oz, was delivered at term by caesarean section

under epidural anaesthesia and appropriate steroid cover.

Comments

Pemphigus comprises a range of rare autoimmune mucocutaneous

bullous conditions that tend to occur in later life and have a higher

incidence amongst Jewish populations (1). Involvement of the oral

mucosa occurs frequently and lesions within the mouth often pre-

cede development of the condition within the skin (1). The bullae of

PV within the mouth soon rupture to produce painful mucosal ero-

sions that restrict eating and drinking. The subsequent development

of skin blistering may involve large surface areas, which can predis-

pose the patient to secondary infection and severe fluid/electrolyte

Oral pemphigus and pregnancy

imbalance that has led to the death of patients with PV. Prior to the

introduction of systemic corticosteroid treatment, the clinical course

of PV was extremely unfavourable and resulted in death in approxi-

mately 90% of suffers (2).

The onset of pemphigus during pregnancy presented a thera-

peutic dilemma that needed to address, not only the bullous disease

itself, but also the altered physiology of pregnancy, maternal

anxiety and possible effects on the developing foetus. The clinician

was faced with a duel challenge, as management of the disease

included not only the potential complications associated with PV,

but also the implications of immunosuppression for both mother

and child. In addition to ongoing problems, maternal considerations

may include the need for regional rather than general anaesthesia

during eventual delivery, if mucosa within the upper airway was

involved. Furthermore, maternal PV could potentially lead to the

foetus or neonate being affected with PV as a result of passive

transfer of maternal IgG antibody to the foetal circulation (3, 4).

The treatment of maternal PV with systemic steroids alone has led

to the delivery of neonates mostly free from complications (3, 5, 6).

Although the risk of both teratogenesis and neonatal adrenal sup-

pression are considered low, steroids should be used sparingly during

pregnancy. Prednisolone alone taken during pregnancy in a patient

with PV may contribute to a low birth weight in an otherwise normal

neonate (5). In another case, a 42-year-old-woman with PV com-

menced prednisolone in the third trimester of her pregnancy (4) and

delivered a still-born infant. The cause of this foetal death remains

uncertain and may in part have been due to the advanced age of the

mother.

High-dose steroid therapy combined with azathioprine was ad-

ministered to two patients diagnosed with PV during pregnancy.

Unfortunately, this approach was associated with delivery of one

neonate with a large surface area of exfoliated skin (7) and one still-

born infant with 10% denuded skin. Autopsy of the first of these

cases suggested that the cause of death may have been due to cyto-

megalovirus pneumonitis secondary to immunodeficiency (7).

Previous reports (3, 6) have suggested that patients with PV who

became pregnant whilst receiving steroids had better control of PV

and pregnancy outcome than those patients in whom normal steroid

treatment was started in late pregnancy (4). Commencement of ster-

oid treatment in the latter stages of pregnancy was associated with

high-dose steroid regimens and the perceived need for adjuvant ther-

apy involving azathioprine, dapsone or cyclosporin. However, the use

of these additional agents has invariably led to the death of the

foetus (7).

When PV has been diagnosed early in pregnancy and treatment

with short-term high dose steroids has been started early, continued

use of high doses of steriods have not been necessary (5). The symp-

123J Oral Pathol Med 31: 121–4

tomatic improvement could, in part, be due to the ability of the

placenta to produce endogenous steroids in the latter stages of preg-

nancy (8). In the initial phase of the illness, steroids are prescribed

at high doses to prevent progression of the disease. As PV is

brought under control, the steroid dose is gradually reduced (2). It

is suggested that further development of PV from oral cavity to

skin is prevented by such an approach.

If suspected clinically, a definitive diagnosis of PV should be

made early as a delay in providing appropriate treatment can lead

to significant complications. Although systemic steroid therapy was

required for the duration of the pregnancy described in this case,

once the patient was symptom free, only a low dose of prednisolone

(5 mg daily) was required to maintain oral health and function. The

potential complications of high dose steroids and uncontrolled PV

were therefore minimised.

Although rare in woman of childbearing age, suspected cases of

oral PV, due to the presence of erosive bullous lesions within the

mouth, require urgent referral to a unit with experience in the man-

agement of such disorders. Steroid regimens used during pregnancy

should be low as possible if started after the first trimester to mini-

mise the risk of teratogenic complications (6). In addition, patients

should be monitored for the standard problems of steroid therapy

such as diabetes mellitus, myopathy, depression and delayed wound

healing. It is important to work closely with the patient’s obstetri-

cian to achieve a joint treatment plan and to ensure adequate post-

partum care of both mother and foetus.

It is concluded that woman known to have PV who are planning

to conceive, should be made aware that close support is available

that might be needed during the pregnancy. Early treatment of PV

can minimise the symptoms and extent of this serious disease,

which is particularly important when occurring during pregnancy.

The number of reported cases of PV in pregnancy is small and it

is not possible to predict the likelihood of recurrence of symptoms in

subsequent pregnancies for an individual patient. Each pregnancy

should be managed appropriately on an individual basis.

References

1. Krain LS. Pemphigus: Epidemiologic and survival characteristics of 59patients 1955–73. Arch Dermatol 1974; 110: 862–5.

2. Lever WF, White H. Treatment of pemphigus with corticosteroids: re-sults obtained in 46 patients over period of 11 years. Arch Dermatol1963; 87: 12–26.

3. Merlob P, Metzker A, Hazaz B, Rogovin H, Reisner SH. Neonatal pemphi-gus vulgaris. Paediatrics 1986; 78: 1102–5.

4. Green D, Maize JC. Maternal pemphigus vulgaris with in vivo boundantibodies in the still-born foetus. J Am Acad Dermatol 1982; 7: 388–92.

Lewis et al.

5. Kanwar AJ, Kaur S, Abraham A, Nanda A. Pemphigus in pregnancy.Am Job Obstet Gynecol 1989; 161: 995–6.

6. Goldberg NS, DeFeo C, Kirschenbaum N. Pemphigus vulgaris and preg-nancy: Risk factors and recommendations. J Am Acad Dermatol 1993;28: 877–9.

7. Ross MG, Kane B, Frieder R, Gurevitch A, Hayahsi R. Pemphigus inpregnancy: a re-evaluation of foetal risk. Am J Obstet Gynecol 1986; 155:30–3.

8. Levitz M, Jansen V, Dancis J. The transfer and metabolism of cortico-

124 J Oral Pathol Med 31: 121–4

steroids in the perfused human placenta. Am J Obstet Gynecol 1978;132: 363–6.

Acknowledgements

The authors wish to thank the staff of the Department of Obstetrics Gynae-cology, Caerphilly Miners Hospital, Caerphilly for their co-operation in themanagement of this patient.