Elisabet Nylander Immunobullous disorders are severe chronic mucocutaneous blistering diseases caused by antibodies directed against skin adhesion molecules. They mainly affect older people and always interfere with quality of life. The most severe cases may even be fatal, a risk that can be reduced by treatment. Blistering diseases are rare, but the incidence seems to be increasing. Vulval involvement is common, occurring in over 50% of patients, and there may be diagnostic difficulty [1]. The diseases include bullous pemphigoid, mucous membrane pemphigoid, pemphigus vulgaris, paraneoplastic pemphigus, dermatitis herpetiformis, and epidermolysis bullosa acquisita. Linear IgA disease is far more common in children and is discussed in Chapter 49. Skin autoimmunity is associated with several factors such as microbiome, heredity, and sex. The diseases can present in different ways but share the similar aetiology of an antibody directed against a specific part of the epidermis or dermo‐epidermal junction [2]. Diagnosis of all immune‐bullous disease is based on a biopsy from the border of a fresh blister, including perilesional skin and subjected to immunofluorescence analysis (see Chapter 7). Antibodies may also be measured in patient sera in the diagnosis of several bullous diseases (Table 26.1), sometimes making biopsies unnecessary. The main difficulty with immunobullous disorders is to distinguish these conditions from one another, and from lichen planus (LP) and lichen sclerosus (LS). The distinction from LS and LP may present difficulty as bullae are readily eroded and may therefore not be visible as such, and the histology may not always be diagnostic. The distinction can be particularly difficult with mucous membrane pemphigoid, in which immunofluorescent findings may be negative. Repeat biopsies, immunofluorescence testing, and panels using sera for indirect immunofluorescence and careful observation will often be required. The appearance of more easily recognisable lesions at other sites can often lend support to a provisional diagnosis. It is always important to consider herpes simplex virus infection, which is usually more acute, but can also complicate immunobullous disorders. Table 26.1 Panel of antibodies against the basal membrane zone and intercellular substance for exploration of patients with bullous diseases (serum samples) Treatment must always be individualised, but due to the low incidence of each of these diseases, this is rarely based on randomised controlled trials. The management of these patients is best planned in multidisciplinary teams in cooperation between dermatologists, oral medicine specialists, ENT specialists, gynaecologists, ophthalmologists, and rheumatologists. Basic dermatological principles of treatment with emollients and therapy for secondary infection, for example with soaks of potassium permanganate, are used. Corticosteroids are generally used as first‐line treatment, either initially applied as ultrapotent topical ointments, or as high‐dose oral preparations. Second‐line systemic immunosuppressive therapy is often needed and emphasises the need for a multidisciplinary approach. A combination of other immunosuppressive agents to reduce the amounts of steroids include, for example, methotrexate, dapsone, azathioprine, mycophenolate, and ciclosporin. Lately there has been a shift of focus from general immunosuppression to targeted immunotherapy such as rituximab, an antibody directed against B‐cells [3,4]. Photopheresis and apheresis to remove or diminish the occurrence of antibodies may also be tried in specialist centres. Close follow‐up and monitoring for medication side effects is mandatory for the successful treatment of the more severe disorders [5]. Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease, accounting for about 80% of subepidermal bullous dermatoses [6,7]. It mainly affects older people, from the age of 70–75 years. BP may also be associated with malignancies [6]. BP is caused by IgG‐antibodies directed against the hemidesmosomal proteins BP180 and BP230. Histopathology demonstrates subepidermal bullae. Direct immunofluorescence shows linear deposits of IgG and C3 at the dermal‐epidermal junction (Figure 26.1), and serum antibodies against BP180 and/or BP230 may be found [7]. Patients present with large bullae and secondary erosions. The bullae are tense, commonly leading to rupture with the formation of erosions, often arising from an erythematous base. Both keratinised and non‐keratinised skin may be involved (Figure 26.2). Up to one third of patients may have oral involvement, and other mucosal sites including the oesophagus, eyes, and nose may also be involved. The pharynx and anogenital region are rarely affected [6]. First‐line treatment is ultrapotent topical corticosteroids and, if not sufficient to resolve the lesions, systemic corticosteroids are used. Treatment often needs to be supplemented with other immunosuppressants such as methotrexate or azathioprine. Starting patients on doxycycline may be an alternative approach to standard treatment with oral prednisolone for short‐term blister control in BP, and it is significantly safer in the long term [8]. There is also often a need for analgesics. Figure 26.1 Direct immunofluorescence (DIF) in bullous pemphigoid – linear band of IgG at the basement membrane. Figure 26.2 Bullous pemphigoid. Tense bullae on an erythematous base. Mucous membrane pemphigoid (MMP) is a chronic, progressive disease that mainly affects the oral mucosa (85%), but also the ocular conjunctiva (symblepharon) in 65%, nasal mucosa in 20–40%, anogenital region and pharynx in 20%, larynx in 5–15%, and oesophagus in 5–15% [4]. Scarring of the anogenital mucosa decreases the quality of life [4]. MMP affects women 1.5–2 times more than men and is most common in persons 60–80 years of age. It can also affect children. Cases that may have been drug induced have also been reported (see Chapter 31). Linear deposition of IgG, IgA, or C3 along the epithelial basement area is seen [4]. Diagnosis involves histopathology and immunofluorescence, which are important to differentiate between diseases with similar clinical and histopathological changes [9]
26
Immunobullous Disease
Diagnosis
Differential diagnosis of the immunobullous disorders
Antibody
Disease
Basal membrane zone (indirect immunofluorescence)
Bullous pemphigoid, unspecified
Intercellular substance (indirect immunofluorescence)
Pemphigus, unspecified
BP 180 (ELISA)
Bullous pemphigoid
BP 230 (ELISA)
Bullous pemphigoid
Desmoglein 1 (ELISA)
Pemphigus foliaceus, pemphigus vulgaris
Desmoglein 3 (ELISA)
Pemphigus vulgaris
Envoplakin (ELISA)
Paraneoplastic pemphigus
Principles of treatment
Bullous pemphigoid
Pathophysiology
Histological features
Clinical features
Treatment
Mucous membrane pemphigoid (cicatricial pemphigoid)
Histological features
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
