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IMMUNOBULLOUS DISORDERS

Introduction

This is an uncommon but important group of disorders, in which there are circulating and tissue antibodies against normal skin structures (Table 16.3). It is important to have some concept of the relevant immunofluorescence testing that confirms these diagnoses, each of which has typical immunopathology features. Two types of test are routinely performed, detailed here; more specialized techniques, such as immunoblotting, are used to confirm the molecular weight of target antigens.

Immunofluorescence tests

Direct immunofluorescence testing

Direct immunofluorescence (DIF) testing (Fig.19.19) is performed on a biopsy of perilesional skin or, in the case of dermatitis herpetiformis, from sites of predilection. The rationale for using perilesional skin is that this is intact, with the normal structures identifiable; blistered skin is more confusing due to the potential for loss of blister roof during processing, and because regeneration changes alter the perceived level of splitting within the skin. In DIF, the biopsy is frozen without chemical fixation and cut into thin tissue sections. These are then incubated with fluorescein-labeled antibodies to detect parts of the section where there has been deposition of immunoreactants such as IgG, IgA, IgM, complement C3, or fibrinogen. In standard use, to increase specificity, two antibodies are applied in sequence, for example rabbit–antihuman IgG followed by a fluorescein-labeled antirabbit immunoglobulin. The specimen is viewed with a fluorescence microscope to localize the region of antibody deposition. Thus, for example, the test may demonstrate that there has been deposition of IgG between epidermal cells (pemphigus) or of IgA at the dermal papillae (dermatitis herpetiformis).

Figure 16.19 Direct immunofluorescence testing. This test detects the patient’s own autoantibodies to a normal structure, shown here using bullous pemphigoid antigen as an example. The circulating autoantibody (1) has passed from the vessels and has bound to the basement membrane zone in vitro (2), and can be identified in the laboratory using an appropriate fluorescein-labeled anti-human antibody (in this case, anti-IgG but other immunoglobulin types or antibodies to detect complement or fibrin may be relevant). This antibody is applied to the histology slide of lesional skin (3) and binds to the autoantibody that has already bound to the bullous pemphigoid antigen (4). Thus the agent that is bound or deposited, and the site binding, can be determined by fluorescence microscopy. (After an original drawing by Dr. N. H. Cox.)

Figure 16.20 Indirect immunofluorescence testing. This test demonstrates that the patient has circulating autoantibodies to a normal structure, shown here using bullous pemphigoid antigen (BPA, a normal component of the basement membrane zone) as an example. The patient’s serum, containing autoantibodies against BPA, is removed as a standard blood sample (1), and is incubated with an appropriate epithelial tissue (human, rodent or monkey skin, esophagus or bladder are all possible substrates depending on the likely diagnosis) (2). The antibodies will bind to the relevant antigens, in this case to BPA in the basement membrane zone (3). The binding can then be identified in the laboratory using an appropriate fluorescein-labeled anti-human antibody, as described for the latter part of the direct immunofluorescence test (4, 5). (After an original drawing by Dr. N. H. Cox.)

    Direct immunofluorescence is relatively crude, as immunoreactants deposited at the dermo–epidermal junction may be targeted at numerous closely adjacent antigens, which cannot be distinguished on routine samples. The technique is therefore often further refined by splitting the skin using saline. ‘Salt-split skin' is cleaved through the lamina lucida of the dermo–epidermal junction, such that the epidermal part has part of the lamina lucida attached, while the dermal part has the lamina densa and part of the lamina lucida (see Fig.16.1). DIF testing on these two parts of the skin will identify the localization of the antibody more accurately. For example, IgG and C3 are deposited at the dermo–epidermal junction in both bullous pemphigoid and epidermolysis bullosa acquisita; in bullous pemphigoid, the deposition is in the lamina lucida and hemidesmosome region (epidermal side of salt-split skin), but in epidermolysis bullosa acquisita the antigen is the anchoring fibrils below the lamina densa (dermal side of salt-split skin).

Indirect immunofluorescence testing

Indirect immunofluorescence (IIF) testing (Fig.16.20) uses much the same technique, but is designed to detect circulating antibodies rather
than those that have bound to tissues, and is therefore performed using a blood sample. The substrate may be human skin, but other species and organs (such as esophagus) can also be used. This is incubated with the patient serum, then with a labeled antihuman immunoglobulin. Positive immunofluorescence identifies that a circulating antibody is present, and also determines the site of binding as already described. This test is, in general, less useful, but in some disorders, such as pemphigus, the titer of positive results may correlate with clinical assessment of disease severity.

Bullous pemphigoid

Etiology and pathogenesis

Bullous pemphigoid (BP) is the most common of the immunobullous disorders but is still rare, with an incidence of about 10 per million per year. The targets for immunologic attack are hemidesmosome proteins known as the BP antigens (Table 16.3). These are derived from keratinocytes, and are mainly found within the basal pole of the basal cells, with a small amount extracellularly in the lamina lucida. A rare 200-kDa target antigen has also been reported. Binding of antibodies, activation of complement, and chemoattraction of neutrophils and eosinophils all contribute to the blistering process.

Clinical

Bullous pemphigoid is primarily a disorder of elderly individuals. Most develop a widespread rash with tense, unilocular blisters of diameter 1–2cm, which contain clear, straw-colored fluid, or are hemorrhagic (Figs 16.21–16.26). A pompholyx pattern of vesicles occurs on the palms and soles in 25% of patients (Fig.16.26). A preceding urticated eczematous phase, often with rather annular lesions, is common and may precede blistering by several months. Oral lesions are uncommon, occurring in about 10–20% of patients, and usually mild if they do occur.

    In about 10–20% of cases, pemphigoid may be localized, for example to a lower leg or around the umbilicus. This causes diagnostic difficulty but may respond to topical treatment alone. A nodular variant also causes diagnostic difficulty.

Figure 16.21 Eczematous lesions are a precursor phase in many patients, but will demonstrate positive immunofluorescence if the diagnosis is suspected and appropriate samples are taken. Clues include an annular morphology (a) and small blisters (b).

Figure 16.22 Localized bullous pemphigoid. This patient had a small crop of blisters on the foot, with positive direct immunofluorescence for IgG and C3. She was treated with topical steroids only and never developed more widespread disease.

Differential diagnosis

This includes the following.

    The diagnosis is established by skin biopsy with DIF: there is a subepidermal blister and deposition of IgG and C3. IIF is less useful, as it is not routinely positive and titers do not correlate with disease activity.

Treatment

Localized BP may be adequately treated with topical corticosteroids, but most patients with generalized disease require systemic corticosteroids. Typically, a dose of about 1 mg/kg per day of prednisolone or prednisone is used initially until new blisters cease to develop, and then reduced every few days in the absence of significant new blisters. The usual risks of these agents, such as fluid retention, hypertension, diabetes, and osteoporosis, are often of particular importance in patients with pemphigoid, who are typically elderly and may have other concurrent illnesses. It is common for additional immunosuppressive therapy to be used, sometimes as monotherapy but more commonly added for its steroid-sparing effect; the usual choice is azathioprine or dapsone, but cyclophosphamide, ciclosporin, mycophenolate mofetil, methotrexate, or intravenous immunoglobulins (IVIG) are also used (see Ch. 4 for monitoring details). A combination regimen of a tetracycline with nicotinamide may also be helpful and less toxic.

Cicatricial pemphigoid

Etiology and pathogenesis

Cicatricial pemphigoid (CP) is due to antibodies that target several potential antigens (Table 16.3).

Clinical

This disorder is twice as common in women as in men. It affects the oral mucosa in 90%, presenting either with blisters and erosions or, commonly, with gingivitis (Figs 16.28–16.32). Conjunctivae are affected in 70%, and are of particular importance due to the development of scarring between bulbar and tarsal surfaces (symblepharon). The skin may be affected in about 20% of patients, often around the scalp, head, and neck; genital mucosa is involved in a similar proportion. Larynx, pharynx, and nasal mucosa may also be affected.

Differential diagnosis

This includes the following.

    Routine histology and DIF will help to distinguish lichen planus and other mucosal lesions; most patients with CP have positive DIF for IgG but may require oral or conjunctival biopsies to demonstrate this.

Treatment

Local measures are used for affected sites, such as steroid mouthwashes and eyedrops. In cases that require systemic therapy, this is as for BP. Ophthalmologic follow-up is recommended. Surgical treatment may be needed to treat ocular or laryngeal scarring.

Figure 16.23 Established bullous pemphigoid involves a mixture of tense clear or hemorrhagic blisters and a variable eczematous background (a–c). (Panel c courtesy of Dr. G. Dawn.)

Figure 16.24 Like the eczematous lesions, blisters may occur in annular arrangements in bullous pemphigoid.

Figure 16.25 Hemorrhagic blisters are a common feature in pemphigoid, shown here on the dorsum of the foot in an elderly man. This is a variant with minimal inflammatory component. In this case, there are tense unilocular blisters but no erythema or eczematous component, a pattern termed cell-poor pemphigoid, as the clinical lack of inflammation is paralleled by a histologic lack of infiltrate. More commonly, as in Fig. 16.23, there is a mixture of inflamed and non-inflamed lesions.

Figure 16.26 Pemphigoid on the extremities tends to produce larger blisters on the dorsa of hands or feet (a), but pompholyx-like lesions on the palmoplantar surfaces (b). Pompholyx-like lesions occur in about 25% of patients, but usually there is relatively extensive pemphigoid blistering at more typical sites. (Panel a courtesy of Dr. G. Dawn.)

Figure 16.27 Blisters due to cellulitis. The elderly lower leg is the commonest site, so pemphigoid is often erroneously considered to be the likely diagnosis.

Figure 16.28 Cicatricial pemphigoid affecting the eye, causing scarring (symblepharon) and severe visual impairment. For this reason, the name benign mucous membrane pemphigoid is something of a misnomer.

Figure 16.29 Gingivitis in a patient with cicatricial pemphigoid. This pattern of periodontal, chronic, red, velvety gingivitis is very suggestive of this disorder but may occur in other blistering diseases (see Figs. 16.38b and 16.59).

Figure 16.30 Cicatricial pemphigoid affecting the tongue. The lesions are rather annular, and may be mistaken for migratory glossitis (geographic tongue, Ch. 20) unless there are other associated features.

Figure 16.31 Involvement of the palate in cicatricial pemphigoid, manifest as purpuric spots. Intraoral lesions of dermatitis herpetiformis may also produce similar purpuric lesions..

Figure 16.32 Cicatricial pemphigoid may affect skin as well as the mucous membranes, usually on the head and neck (termed the Brunsting–Perry type).

Figure 16.33 Pemphigus foliaceus. This typically causes a rather seborrheic eczema–like eruption (a) with some crusting or erosions, rather than frank blisters. However, it is usually more extensive on the face and trunk than would be the case in seborrheic eczema. Some cases of pemphigus foliaceus have a more actively crusted and bullous morphology (b).

Figure 16.34 Pemphigus foliaceus, showing a typical pattern of scattered, crusted patches on the trunk. This variant of pemphigus is often said to respond well to therapy, but personal experience is that it can be a prolonged and difficult condition to manage.

Figure 16.35 Blisters in pemphigus are fragile, as they are due to separation between epidermal cells. Often, the presenting feature is erosions rather than clinically apparent blisters (a). Close-up inspection of pemphigus foliaceous may often reveal similar peeled remnants of blisters among the secondary crusting (b).

Pemphigus

Etiology and pathogenesis

Most pemphigus occurs as an autoimmune phenomenon, with circulating antibodies against desmosomal proteins of the epidermis (Table 16.2). Damage to the desmosomal intercellular attachment causes separation between the keratinocytes, with intraepidermal blistering. It has recently been documented that the same molecule, desmoglein 1, is targeted by auto antibodies in pemphigus foliaceous and by circulating toxin in the SSSS.

Clinical

The main types of pemphigus are listed in Tables 16.5 and 16.6; see also Figs 16.33 –16.43.

    Familial benign pemphigus (Hailey–Hailey disease) is confusingly named; it is a totally different disorder, which is not immunobullous but due to an inherited defect in keratinocyte adhesion by desmosomes (Fig.16.44 and Ch.19).

Differential diagnosis

This includes the following.

Treatment

Most cases require systemic corticosteroids, usually under a fairly aggressive regimen to achieve disease control; initial corticosteroid doses are usually 1–1.5mg/kg per day. In some cases, pulsed doses of intravenous methylprednisolone may be necessary to achieve control of pemphigus. Plasmapheresis may remove circulating antibodies and achieve control, but needs to be used with other therapies to prevent relapse. Many patients will require additional immunosuppressive agents, either to achieve disease control or because the daily steroid dose cannot be reduced to a level appropriate for long-term maintenance. The usual immunosuppressive agents likely to be used are azathioprine, cyclophosphamide, gold, and ciclosporin. IVIG appears to be useful in some cases; other agents that have been used include mycophenolate mofetil, methotrexate, gold, and dapsone. Pemphigus foliaceus is often felt to respond well but can be extremely refractory in some instances.

Figure 16.36 An uncommon, but probably underestimated, variant of pemphigus foliaceus is a type confined to the tip of the nose. As this may respond to topical therapy, and may resolve without recurrence or worsening in some patients, it may be treated more often than it is diagnosed.

Figure 16.37 Pemphigus erythematosus is a rare variant of pemphigus with a very superficial level of blistering and positive antinuclear antibody tests. Extensive facial lesions may occur, with crusting rather than obvious blistering, a pattern that may resemble pemphigus foliaceus, lupus erythematosus (as shown), or seborrheic dermatitis. (Courtesy of James Steger, M.D.)

Figure 16.38 Oral pemphigus vulgaris. Oral involvement commonly precedes skin involvement at other sites, often by several months, and may be misdiagnosed as aphthous, herpetic, or non-specific ulceration initially, as shown in b, affecting the mouth and lip. However, it is usually severe and progressive, which should arouse suspicion about the diagnosis. In some patients, the appearance of oral lesions is that of gingivitis, which may mimic cicatricial pemphigoid, epidermolysis bullosa acquisita, or even lichen planus (see also Figs 16.29 and 16.59). (Panel b courtesy of Dr. G. Dawn.)

Figure 16.39 Pemphigus vulgaris affecting the lip. This eruption followed herpes simplex infection, and Stevens–Johnson syndrome was considered, but biopsy confirmed the diagnosis of pemphigus. Unusually, no other sites were affected over 1 year of follow-up. In this patient, relapses to date have responded to strong topical steroids and have not required any systemic therapy.

Figure 16.40 Pemphigus affecting the tongue. Candidiasis may be difficult to exclude, and is of importance if the patient is already taking steroids or other immunosuppressive therapy.

Figure 16.41 Pemphigus at unusual sites. (a) Mucosae other than that of the mouth may be affected, in this case the eyes ocular conjunctivae . (b) Pemphigus affecting the umbillicus; at this site, unless there is extensive disease elsewhere, it may mimic cicatricial pemphigoid. (Panel b courtesy of Dr. G. Dawn.)

Figure 16.42 Pemphigus vegetans. This affects the major creases such as groins or axillae, and may present as eroded (a) or thickly crusted (b) plaques.

Figure 16.43 The scalp is relatively commonly involved in pemphigus vulgaris, erosions at this site often developing prominent crusting. (Courtesy of Bob Butler, M.D.)

Figure 16.44  Familial benign pemphigus (Hailey–Hailey disease) shares with pemphigus the fact that there is dyscohesion between keratinocytes. However, the mechanism involves an inherently abnormal desmosome rather than an immunologically mediated process. Clinically, the lesions affect mainly the major flexures, and have small surface tears (a) rather than blisters, although the latter are sometimes apparent (b); the disorder is more likely to be confused with eczema than with immunobullous diseases.

PRACTICE POINTS

Paraneoplastic pemphigus

Etiology and pathogenesis

Paraneoplastic pemphigus (PNP) is particularly associated with lymphoreticular tumors. Castleman tumor is disproportionately associated with this disorder, and thymomas may also be found.

Clinical

Paraneoplastic pemphigus may not cause overt blistering. The clinical picture typically includes troublesome cheilitis and conjunctivitis, with an itchy and rather lichenoid papulosquamous eruption at other sites. Palmoplantar lesions occur, and there may be nail dystrophy (Figs 16.45 –16.47). Biopsy features include necrosis of keratinocytes as well as the acantholysis and bulla formation anticipated in pemphigus; immunofluorescence studies are positive, but immunoblotting demonstrates different antigens from those in pemphigus vulgaris or pemphigus foliaceous (Table 16.2).

Differential diagnosis

This includes the following.

Treatment

Treatment of the underlying disorder is the priority, but the disorder may occur as a consequence of advanced lymphomas where previous treatments have failed. In such cases, treatments with systemic steroids as for pemphigus are used, but this is a therapeutically refractory variant of pemphigus.

Figure 16.45 Paraneoplastic pemphigus. Diffuse rash on the trunk, with a rather purple color. Blistering was not a feature in this patient, and lichenoid drug eruption was initially suspected. He was taking various medications for a known lymphoma.

Figure 16.46 Paraneoplastic pemphigus. Acral rash with rather lichenoid or eczematous morphology, and associated nail dystrophy (same patient as in Fig. 16.45).

Dermatitis herpetiformis

Etiology and pathogenesis

Dermatitis herpetiformis (DH) is essentially always associated with the presence of gluten enteropathy, although few patients actually have gastrointestinal symptoms. IgA (of IgA1 type) is deposited in the skin at the papillary tips or in a linear granular pattern at the dermo–epidermal junction at sites of predilection (see later), but the mechanism of its effect is uncertain, as it is demonstrated in non-lesional as well as in lesional skin. Persistence of IgA in the skin for many months after establishing a gluten-free diet may explain the slow response to this treatment, but it is less easy to explain the immediate recurrence of symptoms on inadvertent gluten rechallenge. Nonetheless, the presence of IgA with this distribution pattern on DIF testing is diagnostic.

    Other autoimmune disorders may be associated, such as thyroid disease; one study has shown an increased frequency of diabetes.

Figure 16.47 Paraneoplastic pemphigus (PNP) demonstrating an erosive cheilitis. This is a frequent feature in PNP and often responds very poorly to treatment.

Figure 16.48 Typical sites for dermatitis herpetiformis. (a) The extensor aspect of the forearm near the elbow is classic; note that scabies may produce an almost identical picture at this body site. (b) The ear is an underestimated site; two small intact blisters are present.

Figure 16.49 More florid dermatitis herpetiformis affecting the arms and trunk. At a distance, the lesions suggest eczema or scabies (a), but closer examination (b) shows blistering with an annular morphology. (Courtesy of Dr. G. Dawn.)

Figure 16.50 Dermatitis herpetiformis rarely affects the mouth; when it does, lesions are generally purpuric. (Courtesy of Dr. G. Dawn.)

Figure 16.51 Linear IgA disease on the back, an example with a strikingly annular pattern of involvement.

Clinical

Dermatitis herpetiformis usually affects older children or young adults. Lesions typically occur on extensor elbows and knees, over scapulae, and on the sacrum or buttock. Involvement of scalp, ears, and face are often underestimated, but these are not uncommon sites of lesions. The individual lesions are small and intensely itchy vesicles of a few millimeters in diameter, usually excoriated, and sometimes with a mildly eczematous or urticated background (Figs 16.48 –16.50). Oral and palmar lesions are both uncommon, but both may be purpuric if they occur. Biopsies for DIF can be taken from sites of predilection for that individual (usually extensor aspect of the forearm near the elbow) even in the absence of active rash at the time; complement C3 is often present in addition to the typical IgA deposits.

    Blood tests in DH may be performed for various reasons.

    Frank malabsorption is uncommon, even though partial villus atrophy is usual. There is an association between DH and lymphoma, especially of the small intestine.

Differential diagnosis

Dermatitis herpetiformis may be difficult to diagnose, as the blisters it causes are small, very itchy, and frequently destroyed by scratching. The sites of predilection are diagnostically helpful, but it should be noted that lesions of scabies are also very itchy and are common at the elbow region. The main differentials are as follows.

Treatment

Dapsone is the initial treatment of choice, and has sufficiently dramatic effect on itch within 24h that it is diagnostically useful. Side effects and monitoring are discussed in Chapter 4. Other sulfones, such as sulfapyridine or sulfamethoxypyridazine, may be alternatives to dapsone in some cases.

    A gluten-free diet is also important but takes 6 months or so to work. It is of particular value in patients who require only low doses of dapsone (who may be able to stop all drug treatment), or those in whom adequate dosage is limited by hematologic side effects, but patients in between these extremes often find the diet more difficult than taking dapsone. Strict gluten-free diet reduces the risk of lymphoma.

Linear IgA disease

Etiology and pathogenesis

In linear IgA disease (LAD), there is deposition of IgA (mainly IgA1) at the dermo–epidermal junction, both within the lamina lucida and in
the region of the sublamina densa anchoring fibrils. On DIF, it has a linear distribution that is distinct from DH, and there is no association with gluten-sensitive enteropathy. Most cases are of unknown etiology, but drugs are implicated in some cases (vancomycin, diclofenac, and lithium), and associations have been reported with autoimmune diseases (ulcerative colitis, rheumatoid arthritis, and systemic lupus erythematosus) and with various malignancies.

Clinical

Blisters may resemble DH or BP, and often have an annular arrangement (Figs 16.51 and 16.52). The trunk and limbs are the most common sites. Mucosal involvement is relatively common; the eyes and mouth are each involved in about 50% of cases, occasionally very severely, with scarring and visual impairment (Fig.16.53).

Differential diagnosis

This can usefully be considered according to blister size and presence of mucosal disease.

Figure 16.52 Linear IgA disease (LAD) with blisters on the neck. The slightly annular appearance shown here is suspicious of LAD.

Figure 16.53 Linear IgA disease with scarring of eye and blindness; there was also marked scarring of hands (Fig. 4.15).

Figure 16.54 Chronic bullous dermatosis of childhood causing an impetigo-like blistering eruption on the face. The blisters of impetigo are generally more fragile and cause yellow crusting rather than tense, clear blisters. (Courtesy of Charlie Rosenberg, M.D.)

Figure 16.55 Genital involvement and pubic lesions are typical in chronic bullous dermatosis of childhood, shown here in a child who had been treated for several months for herpes simplex and impetigo. There was a dramatic response to sulfapyridine, with no recurrences after 12 months.

Treatment

Treatment of LAD is usually similar to DH initially, with dapsone or other sulfones. Topical corticosteroids may be useful, and some patients require systemic steroids or other immunosuppressive agents such as cyclophosphamide or azathioprine.

Chronic bullous dermatosis of childhood

Etiology and pathogenesis

Chronic bullous dermatosis of childhood (CBDC) is probably the childhood version of LAD, typically occurring in the first decade of life.

Clinical

Clusters of blisters occur, especially in the genital area and around the mouth, where they may be confused with impetigo (Figs 16.54 and 16.55). In older children, they may be more widespread. Mucous membranes may be affected.

Differential diagnosis

This is the same as for LAD, although it is common for infective causes (impetigo and herpes infection) to head the differential diagnosis list in children; CBDC is rare, and many children are erroneously treated for infection for long periods. Childhood BP (Fig.16.56) may also need to be considered.

Treatment

Treatment of CBDC is similar to that of DH or LAD, but sulfapyridine is probably the treatment of choice. Dapsone is also effective, but it may be difficult to obtain formulations suitable for young children. Corticosteroids and colchicine have also been used with benefit. Remission over a period of a few years is frequent, and the disorder usually remits by puberty.

Figure 16.56 Bullous pemphigoid is rare in children, but can occur and may resemble chronic bullous dermatosis of childhood in having genital involvement, as shown here.

PRACTICE POINTS

Epidermolysis bullosa acquisita

Etiology and pathogenesis

Epidermolysis bullosa acquisita (EBA) is a rare immunobullous disorder that is due to antibodies against a lamina densa or sublamina densa antigen, identified as 290-kDa and 145-kDa proteins by immunoblotting, and now known to be the C terminus of type VII procollagen that forms part of
the anchoring fibrils. Antibody (IgG) and complement C3 deposition is associated with neutrophil-mediated tissue damage.

    Epidermolysis bullosa acquisita is associated with a wide range of other disorders, including the following.

Clinical

Epidermolysis bullosa acquisita may present in two main forms. One is reminiscent of porphyria cutanea tarda, with blisters over trauma sites such as knuckles, skin fragility, and healing with milia. The other pattern, in which skin fragility may also be prominent, is much more suggestive of BP (Figs 16.57–16.59).

Differential diagnosis

This depends on the clinical pattern.

Figure 16.57 Epidermolysis bullosa acquisita resembling porphyria cutanea tarda, in a patient with Crohn disease. There is scarring and milia formation within the lesions.

Figure 16.58 Epidermolysis bullosa acquisita, in this case occurring as a paraneoplastic phenomenon. Fragility of the skin is a typical feature, whatever the cause, and may be very difficult to control. Minor trauma with subsequent shearing of the skin accounted for the bizarre shapes seen here.

Figure 16.59 Erosive gingivitis in a patient with epidermolysis bullosa acquisita. This is clinically indistinguishable from the gingivitis that may occur in cicatricial pemphigoid (Fig. 16.29).

Figure 16.60 Blisters are rare in lupus erythematosus but may cause diagnostic difficulty, particularly in children, as in this case.

    The differential from PNP or SSSS is particularly important in patients with tumor-associated EBA, who may be immunosuppressed by their disease or its treatment, and in whom blistering eruptions may be linked with chemotherapy or infection.

Treatment

Epidermolysis bullosa acquisita is relatively resistant to therapy, and may be very troublesome in patients with significant fragility of the skin. High-dose prednisolone, cyclophosphamide, azathioprine, methotrexate, and ciclosporin are all possible treatment options.

Other autoimmune diseases

Blisters may occur in other inflammatory autoimmune conditions, such as lichen planus (see Fig. 8.20) or lupus erythematosus (Fig.16.60).

White/Cox: Diseases of the Skin, 2ed.(c) 2006, Elsevier Inc. All rights reserved.