Last Updated: 2022-03-11
Bunes, 1811; Milton 1872
Pemphigoid gestationis, Dermatitis multiformis gestationis; Gestational pemphigoid; Hidroa gestationis; Pemphigus gravidarum; PG; Gestational pemphigoid
Rare, autoimmune pregnancy dermatosis with frequent occurrence in the second trimester accompanied by pruritus and uriticaria-like excoriations up to blisters, which can also affect the newborn. An association with chorionic carcinoma or bladder moles has also been described
- Incidence: 1/2000-1/50,000 pregnancies per year, corresponding to an incidence of 2 new cases per million population per year. Current papers tend to assume a higher incidence because of improved diagnostics.
- The average age of onset is 30.5 years
- Occurrence usually in the mid-trimester or immediately after birth
- Ersgravida on average in the 31st week
- Multigravidae on average at 21.2 weeks
- During pregnancy, autoantibodies are formed for unexplained reasons. These mostly mark the 180-kDa (BP 180) "bullous pemphigoid antigen", which corresponds to collagen XVII. The NC16A domain in particular is crucial for the immune response. In 20% of patients, the 230-kDa (BP 230) is affected, which is localised at the hemidesmosomes of the dermoepidermal junction zone. Through the autoantibodies, an immune reaction induced by complements is possible, which can be detected in the pregnant woman as well as in the newborn.
- Patients with HLA-DR3 and DR4 haplotypes are more likely to develop the disease; 50% of fathers have an HLA-DR2 haplotype.
- Disease of the placenta is discussed as a possible cause, with a cross-reaction with target antigens of the skin. The following arguments support this hypothesis:
- Occurrence exclusively in pregnancy, chorionic carcinoma or bladder mole
- The IgG antibodies are also found in the basement membrane of the chorionic and amniotic epithelium
- No case has been described in men with chorionic carcinoma. This could be due to the fact that the initial tissue is syngeneic.
- Immune reaction against paternal plant tamatirix genes is possible due to increased expression of MHC class II molecules (DR, DP, DQ) in the villi of the chorionic villi.
- BP180 is close detectable in the aminone epithelium from the 2nd trimester.
- The also possible skin manifestations of the newborn can be explained by transplacental antibody transfer.
- Prior to skin manifestation, there is generalised pruritus for several days to weeks
- Initial periumbilical grouped or disseminated urticaria-like excoriations, accompanied by marked redness and pruritus, which in the course affect the whole body except the face. A corkadeniform appearance may also occur.
- Size from 0.2-4 cm.
- After a few weeks, the disease progresses and grouped standing vesicles to blisters occur, with the latter being optional.
- A mucosal involvement is uncommon.
- An association with other blistering autoimmune diseases has been described.
- The newborn may also present with dermatological abnormalities similar to those of the mother but with a milder course and resolution within a few weeks. Blistering is not mandatory.
- A marked improvement of the symptoms in advanced pregnancy is typical.
- Aggravation of the complaints shortly before or during birth with the appearance of blisters within a few hours.
- Anamnesis, especially with the question of the time course, previous itching and known autoimmune dermatoses
- Eosinophilia in the blood test
- Histological examination to detect eosinophilia, superepidermal localised blistering and inflammatory cells in the corium.
- Direct immunofluorescence demonstrating C3 complex deposition at the dermoepidermal junctional zone. In 1/3 of patients, IgG, IgA and IgM can also be detected. If the salt-split method is used, epidermal of the salt-split preparation shows complete reactivity of C3. Direct immunofluorescence is also feasible in the newborn with the same result.
- Indirect immunofluorescence for confirmation of circulating antibodies which fix complements in split skin preparations. If possible, the sample should be taken from the bladder roof, as this is where the most pronounced binding of IgG occurs. If an incubation with a complement source is carried out, complement-binding IgG1 (herpes gestationis factor) can be seen in 90% of the samples. Pemphigoid antibodies can also be sought. However, these are only detectable in 20% of those with the disease.
- In the blood, reactivity against the NC16A domain of BP180 can be proven by ELISA or immunoblot.
- In case of persistence or appearance only weeks to months after the birth, a placental tumour should be considered as a differential diagnosis and the corresponding clarifications should be initiated.
Mostly abdomen, especially periumbilical, trunk, and extremities. The face is excluded from the dermatosis. In 20% of patients, the mucous membrane is also affected.
- Transition of herpes gestationis into bullous pemphigoid
- Transient dermatosis also in the newborn (5-10% of cases) due to diaplacental antibody (IgG) transfer
- Preterm birth in the context of placental insufficiency, which is more common in affected individuals.
- Small for Date Babies
- Newborn adrenal insufficiency associated with systemic glucocorticoid treatment of the mother.
- Patients with herpes gestationis have a higher risk of developing Graves' disease.
- The prognosis is good, as the disease generally resolves 2-3 weeks postpartum. At most, the dermatosis persists for 6 months.
- Mother and child are not normally at vital risk from the blistering. There are also no reports of malformations in the newborn. The baby recovers completely from the skin lesions within days to weeks at the most.
- Recurrences can occur with renewed pregnancy, the use of hormonal contraceptives or the start of menstruation after birth.
- When paternity remains constant, the risk of recurrence is significantly increased.
- The therapeutic goal is the suppression of pruritus and blistering
- Initially shaking mixtures, creams or gels without additives in combination with cold douching
- In the absence of effect of the above measures, glucocorticoid-containing emulsions such as 0.5-1% hydrocortisone emulsion can be used
- In severe prurigo, antihistamines can be used systemically. Sedating products should be chosen, which are already considered safe in the first trimester. These include, for example, dimetindene or clemastine. The dosage is 1 tablet per day. In the 2/3 trimester, non-sedating antihistamines such as loratadine, cetericine can also be prescribed
- In cases of blistering or prurigo of such severity that it causes sleep disturbance, non-halogenated glucocorticoids are the treatment of choice. For example, medication with prednisolone in a dosage of 0.3-1.0 mg/kg bw/day p.o. is possible, with the possibility of gradual reduction for optimal dose finding. Most patients respond to a dosage of 0.5mg/kg bw/day p.o.
- In case of resistance to therapy, the use of IVIG or cyclosporine can be discussed.
- Postpartum, shock therapy with cyclophosphamide, plasmapheresis or dapsone can be given. In pregnancy, these options are not suitable.
- System therapy must be increased shortly before birth, as there is then usually an aggravation of the clinic.
- In addition to dermatological therapy, regular and close gynaecological monitoring is indicated. The patient should be connected to a clinic with an infant intensive care unit.
- If symptoms persist for a prolonged period after birth, therapy should be analogous to that for bullous pemphigoid.
- Altmeyer Enzyklopädie, Kapitel Pemphigoid gestationis
- Braun Falco, 5. Auflage, Kapitel Bullöse Autoimmundermatosen, S. 624-626
- Bolognia Dermatology, 3 Edition, Chapter Pregnancy Dermatoses S.439