Inflammatory epidermolysis bullosa acquisita: case report

Abstracts

Apresenta-se caso de epidermólise bolhosa adquirida inflamatória. Paciente do sexo masculino, 53 anos, há seis meses com erupção vesicobolhosa pruriginosa sobre base eritematosa no tronco, axilas e membros. O exame anatomopatológico mostrou bolha subepidérmica com neutrófilos. A imunofluorescência direta revelou depósitos lineares de IgG, IgA, IgM e C3 na zona da membrana basal, sendo a imunofluorescência indireta e o Salt Split Skin indireto negativos. Anticorpos antinucleares não reagentes. Houve melhora do quadro com prednisona e cicatrização de algumas lesões com formação de milia. Trata-se de apresentação rara de epidermólise bolhosa adquirida, com lesões iniciais predominantemente inflamatórias.

Epidermólise bolhosa adquirida; Membrana basal; Vesícula

CASE REPORT

Inflammatory epidermolysis bullosa acquisita – Case report

Marcelo D'Ambrosio Fernandes^I; Mariana Discacciati Chiminazzo^II; Antonio José Tebcherani^III; Valéria Aoki^IV; Ana Paula Galli Sanchez^V

^IPhysician, Specialist in Dermatology, former-resident, Complexo Hospitalar Padre Bento de Guarulhos - Guarulhos (SP), Brazil

IIPhysician, Specialist in Dermatology, former-resident, Complexo Hospitalar Padre Bento de Guarulhos - Guarulhos (SP), Brazil

^IIIMaster in Pathology, Pathologist, Service of Dermatology, Complexo Hospitalar Padre Bento de Guarulhos - Guarulhos - São Paulo (SP), Brazil

^IVPh.D., Professor, Department of Dermatology, Medical School, Universidade de São Paulo - Guarulhos (SP), Brazil

VMaster in Sciences, Dermatologist, Service of Dermatology, Complexo Hospitalar Padre Bento de Guarulhos - Guarulhos (SP), Brazil

Mailing Address

ABSTRACT

We report a case of an inflammatory variant of epidermolysis bullosa acquisita in a 53-year-old male, with itching blistering eruption on the trunk, armpits and limbs for six months. The skin biopsy specimen showed subepidermal blister with neutrophils. Direct immunofluorescence revealed linear depositions of IgG, IgA, IgM and C3 at the basement membrane; indirect immunofluorescence and salt split skin were negative. Antinuclear antibodies were also negative. Improvement of the blisters followed treatment with systemic corticotherapy and some lesions healed with milia. This is a rare presentation of epidermolysis bullosa acquisita, with inflammatory lesions at first.

Keywords: Basement membrane; Blister; Epidermolysis bullosa acquisita

INTRODUCTION

Inflammatory epidermolysis bullosa acquisita (EBA) is a rare clinical variation of EBA with acute onset of erythema-urticaria and vesicle-bullous lesions with marked pruritus ¹. It has the same classical progression, including the possibility of milia formation upon healing ¹. Considering the initial inflammatory pattern and onset in adult age, it is necessary to make differential diagnosis with bullous pemphigoid (BP), dermatosis by linear IgA in adults and bullous systemic lupus erythematosus (BSLE). ^{2, 3, 4, 5}

In EBA, the clinical pathology reveals subepidermal bulla with neutrophilic inflammatory infiltrate ^{1, 6}. Direct immunofluorescence (DIF) shows linear deposits of IgG and C3, and IgA and IgM occasionally present on the basement membrane zone (BMZ) ^{1, 6} with dermal fluorescence of salt-split skin (SS) on DIF and indirect immunofluorescence (IIF) ⁷.

CASE REPORT

Fifty-three-year-old male, brown-skin trader. For six months he had presented tense blisters of serous content, both isolated and clustered, some over annular erythematous-edematous plaques, markedly pruriginous, predominantly on the lateral aspect of the trunk, with progression to the axilla and limbs. He reported new lesions on areas of minimum trauma, such as extensive area of the knees (Figure 1A and 1B). Absence of lesions on the mucosa and associated systemic symptoms.

He reported history of systemic high blood pressure and treatment with losartan, amlodipine and hydrochlorothiazide with amiloride. He had no personal or family history of bullous disease.

The test results were complete blood count with leukocytosis (total leukocyte count of 14,200 leukocytes), number of erythrocytes, complete blood count, platelet count, liver and renal function, electrolytes, fast glucose level, transaminase, canalicular enzymes, electrocardiogram and chest x-ray were normal. Anti-nucleus factor, anti-Sm, anti-Ro, anti-La and anti-DsDNA were not reagent. Complements, ESR, urine I and thyroid function were within normal range.

Clinical pathology of the bullous lesion showed subepidermal cleavage with marked neutrophilic inflammatory infiltrate and rare eosinophils (Figure 2). DIF of perilesional skin revealed marked linear deposits of IgG, IgA, IgM and C3 on the BMZ (Figure 3). IIF and indirect SSS were negative.

Right after beginning of treatment with prednisone 40 mg/day, there was improvement of the presentation with healing of blisters and formation of milia over some scars (Figure 4).

DISCUSSION

EBA is a bullous dermatosis resulting from the formation of anti-collagen VII autoantibodies and associated with HLA-DR2 ^{6, 8}. The presentation normally takes place in adult age (higher incidence at the age of 50), with greater predominance in female patients. It may be associated with other diseases such as diabetes mellitus, thyroiditis, Crohn's disease, systemic lupus erythematosus, lymphoma, pernicious anemia and autoimmune thrombocytopenia ^{1, 9}.

There are two clinical forms: mechanic-bullous (more common) and inflammatory ⁴.

In the mechanic-bullous form, lesions occur in areas of trauma and progress with formation of atrophic scars and milia ⁹. There are frequent lesions in photoexposed areas, which require differential diagnosis with late skin porphyria. There might be mucosa lesions (especially oral mucosa), scarring alopecia and onychodystrophy ⁹. Clinical pathology shows subepidermal bullous, in general without inflammatory component ⁶. DIF shows linear deposits of IgG and C3 on BMZ (occasionally IgA and IgM are also present) ^{1, 6, 9}. Pathogenic autoantibodies are IgG class ¹⁰. IIF is positive in only 50% of the cases and indirect SSS, technique that enhances IIF sensitivity, may be used for diagnosis ¹.

It is worth pointing out that indirect SSS, after healthy skin cleavage (with NaCl solution at 1M) on lamina lucida (LL), uses IIF technique. Thus, it identifies the type of circulating autoantibody on the serum in the patient and it checks the level of correlation between antibodies and auto-antigen (above or below LL). In EBA, immune reagents in indirect SSS occur on the floor of the blister (dermal fluorescence), once collagen VII is found on dense sublamina (DSL) ^{3, 8}3, 8. However, this resource is useful only if IIF is positive. Treatment involves guidance for skin protection against trauma, including systemic drugs, if necessary. We may use prednisone, cyclosporine, dapsone, colchicine, in addition to plasmapheresis and intravenous immunoglobulin ¹.

In the inflammatory form of bullous lesions there may be sudden onset over erythematous or urticaria skin, especially on the trunk and flexures 4. In this type of EBA, blisters may lead to formation of milia and patients have pruritus 9. Differential diagnoses includes BP and dermatosis by linear IgA ^{2, 4, 5}. In inflammatory EBA, subepidermal bullous is rich in neutrophils and it may also contain eosinophils or monocytes ⁶.

Similarly to the mechanical-bullous form, inflammatory EBA in DIF shows linear deposits of IgG and C3 in BMZ, sometimes it has IgA deposits and more rarely it shows IgM deposits ^{6, 9}. The result of DIF in the reported case was compatible with EBA (linear deposits of IgG, IgA, IgM and C3 in BMZ). Other autoimmune bullous dermatoses may happen similar immunofluorescence pattern – bullous systemic lupus erythematous (BSLE) and more rarely BP ^{3, 6}. BSLE is a rare clinical variant of systemic lupus erythematosus ³, but the diagnosis was ruled out because there were no criteria compatible with SLE. BP occurs more frequently in elderly patients and in DIF there are linear isolated deposits of C3 – in all cases – and/or IgG in BMZ ¹. To exclude the diagnosis of BP we collected a blood sample from the patient to perform indirect SSS. In BP, indirect SSS fluorescence is normally epidermal, given that the main target of autoantibodies - the ectodomain BP 180 (NC16A) – is located close to the plasmatic membrane of the keratinocyte, therefore, on the upper LL ¹. In EBA, immune-reagent deposits of indirect SSS occur on the dermal side (floor) of the cleavage.

The indirect SSS of the patient was negative, whose result may have been affected by the use of prednisone. Considering the age range, lesions in trauma area and DIF with deposit of all immune-reagents – which rarely occurs in BP – the diagnosis of inflammatory EBA was made. We could have made DIF SSS, which similarly to indirect SSS, would differentiate EBA from BP based on the location of fluorescence. However, EBA and BSLE have the same pattern, which hinders differentiation.

In inflammatory EBA, the best therapeutic responses are evidenced by systemic corticoid therapy ⁵. In this case, clinical improvement was significant after introduction of prednisone. Currently, the patient has few lesions in trauma areas, controlled by prednisone 10mg/day.

Few cases of inflammatory EBA have been described in the literature to present ^{4, 5, 7, 9}. We have highlighted here the importance of the differential diagnosis of this entity with other auto-immune bullous subepidermal dermatoses, such as BP and linear IgA dermatosis.

REFERENCES

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• 8. Woodley DT, Burgeson RE, Lunstrum G. Epidermolisys bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen. J Clin Invest. 1988;81:683-7.
• 9. Taniuchi K, Inaoki M, Nishimura Y, Mori T, Takehara K. Nonscarring inflammatory epidermolysis bullosa acquisita with esophageal involvement and linear IgG deposits. J Am Acad Dermatol. 1997;36:320-2.
• 10. Woodley DT, Ram R, Doostan A, Bandyopadhyay P, Huang Y, Hemington J, et al. Induction of epidermolysis bullosa acquisita in mice by passive transfer of autoantibodies from patients. J Invest Dermatol. 2006;126:1323-30.

Publication Dates

• Publication in this collection
  03 June 2009
• Date of issue
  Apr 2009