Save S*, Nayak C**, Tambe S***.
(*Registrar, **Professor & Head, ***Assistant Professor, Department of Dermatology, Leprology and Venereology,
B.Y.L. Nair Hospital & Topiwala National
) Mumbai, India
Pemphigoid gestationis is an autoimmune subepidermal bullous disorder typically seen in the second or third trimester of pregnancy, and has very rarely been reported in the postpartum period. The clinical, histopathological and immunopathological features are similar to those of pemphigoid group of disorders. We would like to report a case of PG which presented during the immediate post partum period.
Pemphigoid gestationis (PG) is a rare, self-limited autoimmune bullous disorder that presents mainly in the second or third trimester of pregnanacy or the immediate postpartum period. PG usually presents as urticarial plaques topped with vesicles that subsequently develop into blisters. It is usually associated with severe pruritus and the periumbilical area is commonly the first site to be affected. The face, mucous membranes, palms and soles are usually spared.
A 35 year old housewife presented with multiple red raised lesions topped with fluid filled lesions all over her body of 8 days duration. She indicated that these lesions started appearing 2 days following the delivery of her fourth child by a cesarean section. The lesions, which initially appeared as multiple reddish raised lesions on her limbs, abdomen and neck, were associated with severe pruritus and within 24 hours she noticed the development of multiple fluid-filled blisters over these reddish lesions. The lesions were increasing in size and number since then. She did give history of similar lesions following the delivery of her second child in 2005, but the lesions had resolved spontaneously in the next 15 days. The patient did not have any other significant medical history.
Clinical examination revealed the presence of multiple erythematous urticarial plaques topped with tense vesicles and crusted erosions. (figures 1a & 1b) Lesions were seen mainly over the neck, abdomen, back, upper and lower limbs. Nikolskiy and bulla spread sign were negative. Both the genital and the oral mucosa as well as the palms and soles were spared. Systemic examination was found to be within normal limits.
She had delivered a healthy baby by a cesarean section and the baby did not show any evidence of skin or mucosal lesions.
Routine hemogram, liver and renal function tests and biochemical tests produced normal results and the thyroid hormones were all within normal ranges.
A provisional diagnosis of pemphigoid gestationis was made from these findings.
Histopathology: Two punch biopsy specimens were obtained from the leg from the lesional and perilesional skin for hematoxylin (H) and eosin (E) stain and direct immunofluorescence (DIF) study, respectively. H & E staining revealed a subepidermal split with plenty of eosinophils along with neutrophils in the blister cavity. There was evidence of dermal edema with mixed inflammatory infiltrate in the dermis (figures 2a and 2b). DIF demonstrated a linear deposition of C3 along the basement membrane zone. (figure 3). Thus the diagnosis of Pemphigoid gestationis was confirmed.
Figure 1a. Urticarial plaques on the back topped with vesicles, erosions and crusts.
Figure 1b. Closer view of the vesicles (white arrow)
Figure 2a. Histopathology of skin showing the presence of subepidermal blister. (10X, H & E)
Figure 2b. Blister cavity filled with eosinophils (white arrows). (40X, H & E)
Figure 3. Linear deposition of complement C3 along basement membrane zone seen on Direct Immunofluorescence of perilesional skin biopsy.
Figure 4. Post treatment photograph showing resolution of the lesions.
Treatment: The patient was treated with daily 30 mg of oral prednisolone along with 100 mg of dapsone and antihistamines. There was marked regression in the number of lesions after 1 week. The prednisolone was gradually tapered over the next few weeks to 5 mg per day. She had a relapse after about 3 weeks, with few lesions appearing over extremities and the dose was increased to 10 mg and maintained for the next two weeks following which there was significant improvement, with resolution of existing lesions and no appearance of new blisters. (figure 4)
Apart from its association with pregnancy and puerperium, PG can also very rarely occur in association with trophoblastic tumors like choriocarcinoma and hydatidiform mole. It tends to recur in subsequent pregnancies, with usually earlier onset and increasing severity. Rarely (5%) a pregnancy may not be affected and passed over ("skip pregnancies").[2,3]
The etiology of PG is not entirely understood. It is presumed that auto-antibodies are formed against the placenta, which then cross-react with certain antigens on the basement membrane of the skin. This immune response is mainly directed against the NC16A (noncollagenous) domain of the bullous pemphigoid antigen with a molecular weight of 180 kDa, BP180. Less commonly IgG autoantibodies to BP230 are also present.
Diagnosis is confirmed by the following factors:
(a) Skin biopsy showing the presence of subepidermal blister with eosinophils within blister cavity during pregnancy or in the immediate post-partum period.
(b) DIF reveals the linear accumulation of complement C3 and IgG in the basement membrane zone at the interface of epidermis and dermis.
Measurement of serum BP180 antibody titres correlates with the degree of disease severity.[5,6]
Most patients undergo spontaneous regression over weeks to months postpartum. Recurrent disease flares can occur from 2 weeks up to 12 years postpartum. Recurrence with menstruation or with subsequent use of oral contraceptives has been reported. Fetal risks may also be present and include miscarriages, prematurity, low birth weight babies, transient erythema and blistering.
For mild symptoms, the current guidelines recommend the use of topical potent or very potent corticosteroids combined with the use of oral histamines.
Oral corticosteroids form the first-line systemic therapy of severe pemphigoid gestationis.[8,9] Cyclosporine, tetracycline, cyclophosphamide, azathioprine, dapsone and rituximab are some ot the other treatment options. Plasmapheresis, immunoadsorption and intravenous immunoglobulin G-infusion, have in some cases been used to treat PG prior to delivery.[11,12,13,14]
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