Bullous pemphigoid

Classification according to ICD-10
L12.0	Bullous pemphigoid
ICD-10 online (WHO version 2019)

When bullous pemphigoid (from the Latin. Bullous , vesicular and ancient Greek. Pemphix , bladder) is a blistering skin disease . This disease causes plump, subepidermal blisters that can form on reddened or normal skin. With direct immunofluorescence , autoantibodies against certain structural proteins of the basement membrane can be detected microscopically. The mucous membranes are mostly spared.

Other names for this skin disease are parapemphigus , old age pemphigus , pemphigus with subepidermal blistering , dermatitis herpetiformis senilis , erythema bullosum chronicum

distribution

Bullous pemphigoid is the most common autoimmune blistering disease of the skin with an annual incidence of 0.7 to 1.8 new cases per 100,000 inhabitants . The incidence increases significantly from the age of 60, with men being more frequently affected than women. In men over 90, the number of new cases is 40 per 100,000 inhabitants.

This condition occurs more frequently with other autoimmune diseases such as B. polymyositis , ulcerative colitis or chronic polyarthritis ( rheumatoid arthritis ).

root cause

The cause are autoantibodies, mostly of the IgG group , which are directed against bullous pemphigoid antigen 1 (BP 230) and bullous pemphigoid antigen 2 (BP 180, also known as collagen XVII ). The numbers behind the names of the antigens indicate the molar mass in kilodaltons , which is 230 or 180 kDa.

The bullous pemphigoid antigens are anchoring proteins as components of the hemidesmosomes (basal keratinocytes), which connect the epidermis (epidermis) with the basement membrane. The basement membrane in turn is the connecting layer between the epidermis (upper skin) and the dermis (dermis). The antigen-antibody complex activates the complement system in a type II allergic reaction .

Inflammatory cells ( macrophages and monocytes ) are now attracted to this area. These begin with the destruction of the areas marked as sick by the immune system. The inflammatory cells contain tissue-dissolving enzymes ( proteases ), which destroy the bullous pemphigoid antigens marked by the autoantibodies. A functioning cohesion of the keratinocytes lying on the basement membrane is no longer guaranteed.

Clinically, the loss of cohesion can lead to the accumulation of water in the layer between the lowest epidermal cells and the basement membrane, resulting in blistering. This autoimmune process can occur for no apparent reason or in connection with a paraneoplastic syndrome in tumors (e.g. prostate or bronchial carcinoma ), drugs (e.g. diuretics , penicillin , ACE inhibitors , non-steroidal anti-inflammatory drugs , locally applied fluorouracil ) or UV radiation .

Clinical picture

The main symptom of bullous pemphigoid is the plump (firm) bladder . As a prodrome of the disease, itching can occur without visible changes to the skin ( pruritus sine materia ). A wheal ( urticaria ) preceding the blistering is possible. The bulging blisters are typically located on red, flat erythema . Because of the thick roof of the bladder (entire epidermis), the blisters do not burst easily. After the blisters burst, erosions develop , which usually heal well without the formation of scars or milia. The disease develops spontaneously and has a relapsing and relapsing course. Although blistering is the main symptom, it can be absent in exceptional cases.

Changes in the oral mucous membrane occur in only 20 to 30% of cases and show a low tendency to heal; however, food intake is little or no impaired (in contrast to pemphigus vulgaris). The Nikolsky phenomenon II is positive, the Nikolsky phenomenon I can be positive in the vicinity of the herd, but is otherwise negative.

The general well-being is not impaired in the absence of complications. Complications can be pyoderma , i.e. all skin diseases caused by staphylococci or streptococci . Bullous pemphigoid is mainly localized on the flexor sides of the extremities, in the armpits, and in the intertrigines.

Diagnosis

The main diagnostic tools consist of histology, direct and indirect immunofluorescence , further blood tests and a tumor search.

histology

In the histologically examined sample excision of the skin, two variants of bullous pemphigoid can be distinguished: a cell-rich variant with an abundant mixed-cell inflammatory infiltrate and a cell-poor variant with little to no inflammatory infiltrate. In both variants there is a subepidermal blistering, the roof of the bladder consists practically of the entire epidermis (upper skin). A diagnostically valuable sign is the linear arrangement of leukocytes and nuclear debris at the dermo-epidermal junction.

Direct immunofluorescence

The main IgG and complement C3 in the dermato-epidermal junction zone is detected using fluorescent anti-antibodies. Antibodies of the IgA or IgM type can also be detected in 20% of the patients.

Indirect immunofluorescence

80 to 90% of patients are positive for circulating autoantibodies (pemphigoid antibodies) against basement membrane components.

Laboratory tests

The rate of sedimentation may increase and the blood may show peripheral eosinophilia or IgE-type immunoglobulins may be increased.

Tumor search

Since the bullous pemphigoid can occur in connection or as a consequence of a tumor, a tumor search should be carried out. In this regard, examinations such as an X-ray of the thorax, an ultrasound of the abdomen and a stool blood test are useful and informative .

therapy

Local / external therapy

Topical therapy to be applied to the skin consists of steroids and local antiseptics . As a local antiseptic, 0.5–2% clioquinol cream (e.g. Linola-sept), cadexomer iodine (Iodosorb ointment) or alternatively ethacridine lactate ointment can be used. In addition, the bubbles are opened and punctured in a sterile manner.

Internal therapy

Basically, patients with bullous pemphigoid, with the exception of localized bullous pemphigoid, need internal glucocorticoids (first-line agents), e.g. B. Prednisolone 80-100 mg / day. This is combined with azathioprine at a dose of 100–150 mg / day.

In the case of moderate severity, the initial dose of prednisone is, for example, 1.5-2.0 mg per kg body weight per day (intravenous). The accompanying therapeutic agent of first choice is azathioprine, which, like prednisone, is given in doses of 1.5–2.0 mg per kg of body weight. In addition, a thiopurine methyltransferase deficiency should be ruled out beforehand in order to avoid possible myelosuppression and the therapy should take place under gastric protection. When the condition stabilizes, the azathioprine dose remains and the glucocorticoid is slowly reduced; from <50 mg prednisone equivalent, this can be given orally. After five to seven months is Auslassversuch made deposed in which only azathioprine and then the Glukortikoid is tapered off. If there is a later recurrence after healing, treatment is continued with glucocorticoids and azathioprine, as at the beginning.

If there is no improvement during therapy, azathioprine can be exchanged for cyclophosphamide . Ciclosporin A is available as a reserve therapeutic. In addition, shock therapy with glucocorticoids 500–1000 mg iv can be tried if therapy is resistant. Ultimately, the very expensive and only highly successful therapy with immunoglobulins can be tried. This therapy is also usually combined with glucocorticoids.

The therapy option with dapsone or tetracyclines described in some cases is unsuitable as a standard therapy recommendation .

research

According to one study, doxycycline could be a suitable first-line therapy.

literature

Alexander Meves: Dermatology intensive course. Urban & Fischer at Elsevier, 2006, ISBN 3-437-41162-4 .
Peter Fritsch: Dermatology and Venereology Springer Textbook, 2004, ISBN 3-540-00332-0 .
Peter Altmeyer: Springer Encyclopedia Dermatology, Allergology, Environmental Medicine. Springer, 2002, ISBN 3-540-41361-8 .
B. Braun: Bullous pemphigoid - first manifestation with the picture of dyshidrotic hand and foot eczema and prurigo nodularis. In: The dermatologist . (2002) 53, pp. 739-744.

Web links

Pictures of the bullous pemphigoid on dermis.net

Individual evidence

↑ Jainta et al: diagnosis and therapy of bullous autoimmune diseases of the skin. In: Deutsches Ärzteblatt . 2001; 98, pp. A1320–1325 (PDF; 453 kB)
^ Hywel C Williams, Fenella Wojnarowska, Gudula Kirtschig, James Mason, Thomas R Godec: Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomized controlled trial . In: The Lancet . tape 389 , no. 10079 , April 22, 2017, ISSN 0140-6736 , p. 1630-1638 , doi : 10.1016 / s0140-6736 (17) 30560-3 ( elsevier.com [accessed April 22, 2017]).

[1] Jainta et al: diagnosis and therapy of bullous autoimmune diseases of the skin. In: Deutsches Ärzteblatt . 2001; 98, pp. A1320–1325 (PDF; 453 kB)

[2] Hywel C Williams, Fenella Wojnarowska, Gudula Kirtschig, James Mason, Thomas R Godec: Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomized controlled trial . In: The Lancet . tape 389 , no. 10079 , April 22, 2017, ISSN 0140-6736 , p. 1630-1638 , doi : 10.1016 / s0140-6736 (17) 30560-3 ( elsevier.com [accessed April 22, 2017]).