INTRODUCTION

Bullous systemic lupus erythematosus (SLE) is a rare,distinctive subepidermal blistering disorder that occurs insystemic lupus erythematosus.1 It is characterized clinicallyby a pemphigoid-like eruption with tense fluid-filled vesiclesand bullae, often with a background of maculopapular orurticated erythema. It can affect any area of the body, includ-ing non-sun-exposed sites and the mucous membranes.Pruritus is usually present in variable severity. The lesionsform erosions and crusts before healing, usually but notinvariably without scarring. It affects young women of allraces who have clinical and laboratory criteria of SLE asdefined by the American Rheumatism Association. We reporta typical case and compare the features of this distinctive erup-tion with SLE with blistering and the subepidermal blister-ing disorders.

CASE REPORT

A 19-year old female presented in December 1998 with a 6month history of mouth ulcers, fatigue, facial rash, alopecia,arthralgias and Raynauds phenomenon. A diagnosis ofsystemic lupus erythematosus was made on clinical, sero-logical and kidney biopsy evidence. At the time of diagnosis,she complained of a pruritic, erythematous rash in the peri-umbilical region. She was empirically treated forpresumed candidiasis with a topical antifungal preparation.One month later she presented with an increasingly severe and widespread recurrent, pruritic, erythematousrash associated with a few small blisters in the peri-umbilical region, axillae and a small area of the back. Therewas no history of mechanical fragility of the skin. Her pastmedical history included autoimmune idiopathic thrombo-cytopenic purpura (diagnosed in 1993) requiring splenectomyin 1996. Current medications included penicillin 250 mg twice daily (antibiotic prophylaxis following her splenec-tomy), the oral contraceptive pill (ethinyloestradiol 30 g,gestodene 75 g) and prednisone 20 mg daily (commenced onthe diagnosis of SLE). On presentation, there were numerousbullae and vesicles on a background of urticated plaquesaffecting the back, abdomen, the lateral neck and flexures ofthe arm and groin regions (Fig. 1). Nikolskys sign was neg-ative. Older lesions were characterized by erosions withcrusts. No scarring was seen at the sites of healed lesions.There were no mucosal erosions or blisters. She hadCushingoid features.

Investigations revealed an erythrocyte sedimentation rateof 53 mm/hour (normal range (NR), < 20 mm/h), antinuclearfactor 1:128 (speckled pattern), anti-dsDNA 500 IU/mL (NR,< 7 IU/mL), positive anti-Ro, La, RNP, Sm and Jo-1 antibodies.Her C3 was low at 0.31 g/L (NR, 0.81.7 g/L) with C4 0.1 g/L(NR, 0.20.6 g/L) and total complement (CH100) < 20 U (NR,40150 U) but C3 activation was negative. Complete bloodcount, serum creatinine and C-reactive protein were normal.Indirect immunofluorescence (IIF) on serum taken prior tothe commencement of prednisone was negative for skin anti-bodies.

Histology of punch biopsies of entire blisters taken from theabdomen showed prominent inflammation at the dermo-epidermal junction with a band-like neutrophilic infiltrate andsubepidermal blister formation (Fig. 2). In other areas,papillary neutrophilic microabscesses and vacuolization withbasal degeneration of the epidermis and early blisterformation was seen. Peri-appendageal inflammation was alsoseen. Direct immunofluorescence (DIF) showed strongly

Australasian Journal of Dermatology (2000) 41, 234237

CASE REPORT

Bullous systemic lupus erythematosus

Anthony Yung and Amanda Oakley

Department of Dermatology, Waikato Hospital, Hamilton, New Zealand

SUMMARY

A 19-year-old woman with a 6 month history of sys-temic lupus erythematosus (SLE) developed a wide-spread urticated, erythematous eruption associatedwith tense, fluid-filled blisters, erosions and crusting.Biopsy showed subepidermal blistering with a prom-inent neutrophilic infiltrate. Direct immunofluor-escence showed markedly positive granular IgGdeposition with weak IgM, IgA and C3 at the dermo-epidermal junction. No circulating antibodies weredetected on indirect immunofluorescence. A diagnosisof bullous systemic erythematosus was made.Treatment with prednisone was ineffective. Subsequenttreatment with dapsone led to rapid sustainedremission of skin symptoms. Bullous SLE is a raremanifestation of SLE. We review the recent literatureand discuss the distinctive features of this condition andcontrast them with cutaneous SLE with blisters andthe subepidermal blistering disorders.

Key words: collagen, dapsone, immunohisto-chemistry.

Correspondence: Dr Anthony Yung, 7 Pamela Place, St Heliers,Auckland, New Zealand. Email: ayung@ihug.co.nz

Anthony Yung, MbChB. Amanda Oakley, FRACP. Submitted 7 January 2000; accepted 10 April 2000.

Bullous systemic lupus erythematosus 235

positive granular deposition of IgG on the basement mem-brane zone and weak positivity for IgM, IgA and complementdeposition on the basement membrane zone. Indirect im-munofluorescence of salt-split skin was not performed. A diag-nosis of bullous SLE was made.

Increasing the dose of oral prednisone to 60 mg appearedto be unhelpful. The addition of dapsone 50 mg daily initiallyled to marked improvement, although recurrence of bullouslesions occurred 1 week later. An increase in dose of dapsoneto 100 mg daily resulted in 95% clearing of the eruption withindays. Nine months after diagnosis she was free of skin symp-toms on dapsone 100 mg daily and prednisone 6 mg daily.

DISCUSSION

Blisters developing in patients with SLE raises two majordifferential diagnoses: bullous SLE and SLE with blisters.14

Lesions of SLE with blisters are polycyclic with an advancingblistering border. The lesions occur mainly on the face, neckand upper arms, often on sun-exposed sites. The clinicalappearances may mimic erythema multiforme and toxic epi-dermal necrolysis.

Histologically, bullous SLE is a subepidermal blisteringdisease with an acute neutrophil-predominant infiltrate in theupper dermis.17 Papillary microabscesses or a band-likeneutrophilic infiltrate may be present, as seen in our case. Incontrast, the histology of cutaneous lesions of SLE with blis-tering reveals severe oedema in the upper dermis andhydropic degeneration of the basal layer. Epidermal necrosisis seen at the advancing edges of the lesions. A patchy dermaland peri-appendageal lymphocytic infiltrate may be presentin addition to these changes.

Immunohistochemically, DIF of bullous SLE demonstrateslinear or granular deposition of IgG (with or without IgAand/or IgM) and complement deposition at the basementmembrane zone. Indirect immunofluorescence of serum maydemonstrate circulating antibodies to type VII collagen. Theseantibodies usually demonstrate binding to the dermal side ofsalt-split skin preparations on IIF. These antibodies arethought to be pathogenic because type VII collagen is a majorcomponent of the anchoring fibril, which has a central rolein the generation of basement membranedermal adhe-sion.810 It is thought that immune complexes binding to typeVII collagen or complement mediated damage to type VII collagen impairs anchoring fibril function and leads to sub-epidermal blister formation.47 A number of other immuno-histochemical variants have been described.46,11 In contrast,DIF of SLE with blistering demonstrates IgG with IgM (withor without IgA) and complement deposition on the basementmembrane. Circulating antibodies towards type VII collagenare not present. Blister formation is thought to arise fromsevere damage to the basal layer leading to separation fromthe basement membrane. Ultraviolet radiation, high titres ofanti-Ro antibodies, immune-complex deposition and abnor-mal cell mediated immunity are thought to be responsible forthe damage to the basal layer.

Other blistering diseases which may present with similarclinical features to bullous SLE are summarized (Table 1).1,4,7

Dapsone is the mainstay of treatment of bullous SLE.17,12

The response is usually dramatic with cessation of new blisterformation within 12 days and healing of existing lesionswithin several days. Relatively low doses (2550 mg daily) maybe efficacious in some cases. The condition is not particularlyresponsive to systemic corticosteroids as demonstrated by ourcase. Azathioprine, antimalarials and cyclophosphamide have

Figure 1(a) and (b) Lesions of bullous systemic lupus erythema-tosus: vesicles, bullae, erosions and crusted lesions on a backgroundof urticated erythema.

Figure 2 Histology of bullous systemic lupus erythematosus: subepidermal blister with band-like superficial dermal inflammatoryinfiltrate. Fibrinous exudate and neutrophils can be seen within theblister (H & E).

236 A Yung and A OakleyT

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REFERENCES

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2. Rowell NR, Goodfield MJD. The connective tissue diseases. In:Champion RH, Breathnach SM, Burns DA, Burton JL (eds).Textbook of Dermatology, Vol. 3, 6th edn. Oxford: BlackwellScience, 1998; 2437575.

3. Mascaro JM, Herreto C, Hausmann G. Uncommon cutaneousmanifestations in lupus erythematosus. Lupus 1997; 6:12231.

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5. Gammon WR, Briggaman RA. Bullous SLE. A phenotypicallydistinctive but immunologically heterogeneous bullous disorder.J. Invest. Dermatol. 1993; 100: S28S34.

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8. Burgeson RE, Lunstrum GP, Rokosova B. The structure andfunction of type VII collagen. Ann. N.Y. Acad. Sci. 1990; 580:3243.

9. Bchinger HP, Morris NP, Lunstrum GP et al. The relationship ofthe biophysical and biochemical characteristics of type VIIcollagen to the functional anchoring fibrils. J. Biol. Chem. 1990;265: 10 095101.

10. Gammon WR, Murrell DF, Jenison MW et al. Antibodies to typeVII collagen recognise epitopes in a fibronectin-like region of thenoncollagenous (NC1) domain. J. Invest. Dermatol. 1993; 100:61822.

11. Chan LS, Lapiere J-C, Chen M et al. Bullous systemic lupuserythematosus with autoantibodies recognising multiple skinbasement membrane components, bullous pemphigoid antigen 1,laminin 5, laminin 6 and type VII collagen. Arch. Dermatol. 1999;135: 56973.

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