Inflammatory Epidermolysis Bullosa Acquisita Effectively Treated with Minocycline

Abstract

Epidermolysis bullosa acquisita (EBA) is an autoimmune mechanobullous disease that is clinically characterised by blisters and erosions on the skin and mucous membranes (1). Patients with EBA exhibit autoantibodies to type VII collagen (2) and are usually treated with corticosteroids, immunosuppressive agents, colchicine, diaphenylsulfone (DDS), or intravenous immunoglobulin (IVIG); however, to our knowledge, minocycline has not been reported to be effective in such cases. In the present report, we describe a patient with EBA who was initially treated with corticosteroids, and then successfully treated with minocycline for recurrence of EBA following corticosteroid dose reduction. The histological examination of the skin eruptions indicated subepidermal bulla formation as well as infiltration of lymphocytes, eosinophils and neutrophils in the upper dermis. As minocycline is known to inhibit neutrophil and eosinophil recruitment as well as cytokine production, it may be considered as a therapeutic option for EBA, particularly in cases exhibiting infiltration within the skin lesion on histological examination. CASE REPORTA 71-year-old Japanese woman, weighing 44 kg, presented with a 1-month history of many bullae with slight itch on the skin over her entire body (Fig. 1a) and on the tongue (Fig. 1b) and oral mucosa. She had no history of allergy, and the laboratory data were within the normal ranges, including the leucocyte count (6,390/μl; normal range: 3,000-7,900/μl), eosinophil count (198/ μl; normal 100-500/μl) and IgG concetration (1,188 mg/dL; normal 890-1,850 mg/dL). Antinuclear antibodies were negative. Histological examination indicated subepidermal bulla formation along with infiltration of lym phocytes, eosinophils, and a small amount of neutrophils in the upper dermis ( Fig. 1c and d).Direct immunofluorescence (IF) examination of a biopsy specimen from erythema indicated the deposition of immunoglobulin (Ig) G and C3 at the basement membrane zone with u-serrated pattern (3). Indirect IF using 1 M NaCl-split normal human skin sections showed IgG anti-basement membrane zone antibodies, which reacted with the dermal side. Using an enzyme-linked immunosorbent assay (ELISA: MBL, Nagoya, Japan), the titres of IgG antibody to type VII collagen were 76.7 and 146.6, at the first consultation and 2 weeks after the first consultation, respectively (Fig. 2). Antibodies to desmo glein 1 and 3, bullous pemphigoid (BP) 180, and BP 230 were not detected in the patient's serum by ELISA. Based on the clinical features, histopathological findings, IgG deposition at the basement membrane zone, and presence of IgG antibodies to type VII collagen in serum, we diagnosed the patient with EBA. Although the patient was then treated with prednisolone (45 mg/day), the new development of bullae was still noted. The addition of cyclosporine (150 mg/day) to the regimen inhibited the formation of new bullae, and the prednisolone dose could be gradually reduced. However, during this dose reduction period, when the patient was being tr...

A man with a widespread bullous eruption

“…Besides corticosteroids, colchicine and dapsone are often used to treat mild cases of EBA, while for recalcitrant, or severe cases of EBA, immunosuppressive drugs such as methotrexate, cyclosporine, azathioprine, mycophenolate mofetil or cyclophosphamide are employed 1,2,4 . Minocycline was effective in one case unresponsive to corticosteroids and cyclosporine 5 . In cases not responsive to the combination of corticosteroids and immunosuppressive drugs, IVIg can be used at a dosage of 2 g/kg/cycle for 3 days or 0.4 g/day for 5 consecutive days 1,4,6 .…”

“…1,2,4 Minocycline was effective in one case unresponsive to corticosteroids and cyclosporine. 5 In cases not responsive to the combination of corticosteroids and immunosuppressive drugs, IVIg can be used at a dosage of 2 g/ kg/cycle for 3 days or 0.4 g/day for 5 consecutive days. 1,4,6 Rituximab is also used in monotherapy or combined with immunosuppressive drugs in severe cases of multidrug-resistant EBA.…”

Canine epidermolysis bullosa acquisita: a retrospective study of 20 cases

“…Other successful treatment modalities have been reported in scattered reports of human and canine EBA. Such modalities included intravenous immunoglobulins, steroid pulse therapy, ciclosporin (reviewed in) and minocycline . Finally, as 45% of the dogs reported in this study were one year of age or younger, a comparison of treatment outcome with paediatric EBA was attempted.…”

Consensus on the treatment of autoimmune bullous dermatoses: bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita - Brazilian Society of Dermatology

“…91 A recent case report showed a patient with an inflammatory form of EBA who was treated with various therapeutic options, such as systemic corticosteroid, cyclosporine, and dapsone, responding to the combination of minocycline (200mg/day) and systemic corticosteroid. 112 This study suggested that minocycline may be considered as a therapeutic option in EBA, mainly as an adjuvant in inflammatory forms of the disease.…”

“…Minocycline is a broad-spectrum tetracycline that inhibits the recruitment of neutrophils and eosinophils as well as cytokine production. 112 A Japanese study that evaluated the clinical and immunological aspects of 105 patients with EBA described minocycline as one of the most common therapeutic options, having been used in 16 patients; however, details regarding the therapeutic response were not specified. 91 A recent case report showed a patient with an inflammatory form of EBA who was treated with various therapeutic options, such as systemic corticosteroid, cyclosporine, and dapsone, responding to the combination of minocycline (200mg/day) and systemic corticosteroid.…”