Pediatric dermatology Series Editor: Camila K. Janniger, MD Bullous Systemic Lupus Erythematosus With Lupus Nephritis: A Rare Case of a Subepidermal Bullous Disorder in a Child Shital Poojary, MD, FCPS, DNB; Sama Rais, MBBS Bullous systemic lupus erythematosus (BSLE) characterized by a distinct constellation of clini- is a rare subset of systemic lupus erythemato- cal, histologic, and immunologic features.1 Bullous sus (SLE) with bullous lesions in a case fulfilling the systemic lupus erythematosus is extremely rare in American Rheumatism Association (Atlanta) crite- children.2 We report a case of a 9-year-old Indian girl ria, histologically characterized by a neutrophil- with BSLE and lupus nephritis; we review the clinical predominant infiltrate in theCUTIS upper dermis with features as well as the etiopathogenesis of BSLE. immunoglobulin (IgG, IgA, IgM) and C3 deposi- tion at the basement membrane zone (BMZ). It Case Report often is associated with autoimmunity to type VII A 9-year-old girl presented with a blistering eruption collagen (NC1 [noncollagenous domain 1] over her chest, back, arms, and neck of 15 days’ dura- domain), although occasionally other antigens tion; swelling around the eyes and feet of 15 days’ such as laminin 5, laminin 6, and BP230 (bullous duration; and a low-grade fever of 2 months’ dura- pemphigoidDo antigen) have beenNot described. Bullous tion. PhysicalCopy examination revealed multiple tense systemic lupus erythematosus is extremely rare vesicles and bullae overlying urticarial plaques on in children. the neck, chest (Figure 1), back, and arms with no We report here a case of a 9-year-old girl with mucous membrane involvement. The Nikolsky sign BSLE as an initial presentation with lupus nephri- was negative. Other findings on physical examination tis class III, a rare occurrence at such a young included cervical, inguinal, and axillary lymphade- age. Despite the rarity, we suggest that BSLE nopathy; bilateral pitting pedal edema; periorbital should be considered in the differential diagno- edema; and hepatosplenomegaly. A differential diag- sis of subepidermal bullous diseases in children nosis of chronic bullous disease of childhood, child- in view of associated potentially serious sys- hood bullous pemphigoid, bullous drug eruption, and temic manifestations. BSLE was considered. Cutis. 2012;89:17-21. A skin biopsy showed subepidermal bullae con- taining proteinaceous debris with predominantly neutrophils, neutrophilic nuclear dust, basal cell ullous systemic lupus erythematosus (BSLE) is vacuolization, and papillary dermal edema (Figure 2). a rare nonscarring subepidermal bullous erup- Direct immunofluorescence of perilesional skin B tion in systemic lupus erythematosus (SLE) showed a broad granular band of IgG deposits at the dermoepidermal junction (DEJ). IgM, IgA, and C3 From K.J. Somaiya Medical College, Mumbai, India. were negative. Direct immunofluorescence of a renal The authors report no conflict of interest. Correspondence: Shital Poojary, MD, FCPS, DNB, Department of biopsy showed IgG deposits at the basement mem- Dermatology, K.J. Somaiya Medical College, Everard Nagar, brane zone (BMZ). IgM, IgA, and C3 were negative. Sion-Chunnabhatti, Mumbai -400022, Maharashtra, India. Electron microscopy of a renal biopsy showed mild WWW.CUTIS.COM VOLUME 89, JANUARY 2012 17 Copyright Cutis 2012. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Pediatric Dermatology albumin 31 (2 g/dL); occult blood 21 (red blood cell count, 15–20 per high-power field [HPF]); pus cells, 3 to 4 per HPF; hyaline casts, 1 to 2 per HPF; and granular casts, 1 to 2 per HPF. Total urinary protein excretion was 1.5 g per day. Chest radiograph showed fissural effusion. Ultra- sonography of the abdomen showed mild hepa- tosplenomegaly; electrocardiography revealed no abnormalities; antinuclear antibody was positive with a titer of 1:40 (reference range, 1:20); anti-dsDNA was high, 1:20 (reference range, 1:10); and serum C3 levels were low, 11.2 mg/dL (reference range, 88– 200 mg/dL). Enzyme-linked immunosorbent assay for human immunodeficiency virus was nonreactive. Figure 1. Grouped vesicles and bullae overlying urti- Tests for antibodies to type VII collagen were not carial plaques on the neck and upper chest. done due to lack of availability. In view of renal involvement, she was treated with oral prednisolone at a dosage of 1 mg/kg daily, which was tapered over the following 2 months. The cutaneous lesions resolved within 2 weeks. Renal parameters showed considerable improvement along with a rise in complement levels. Comment Bullous lesions in SLE are uncommon (,5% of SLE patients) and are divided into 3 categories1,3: CUTIS(1) severe basal cell vacuolization, dermal edema, and leukocytoclastic vasculitis may occasionally manifest as frank vesiculation (eg, subacute cutaneous lupus erythematosus with erythema multiforme–like lesions [Rowell syndrome]); (2) a number of primary blister- ing disorders such as dermatitis herpetiformis (DH), bullous pemphigoid, pemphigus vulgaris, pemphigus Do Notfoliaceus, Copy epidermolysis bullosa acquisita (EBA), and Figure 2. Subepidermal bulla with a predominantly neu- linear IgA bullous dermatosis have been reported in trophilic infiltrate and neutrophilic nuclear dust. Basal cell vacuolization also was noted (H&E, original magnifi- association with SLE; and (3) BSLE. cation 3100). The first case of BSLE was described by Pedro and Dahl4 in 1973. Bullous systemic lupus erythematosus typically affects young adults, chiefly women, often of African and Hispanic descent. It generally presents as mesangial hypercellularity with subendothelial depos- an acute-onset, generalized, vesicobullous eruption, its. Routine investigations revealed the following varying from grouped herpetiform vesicles to large results: hemoglobin, 8.3 g/dL (reference range, 11.5– hemorrhagic bullae that heal without scarring. How- 14.5 g/dL); total white blood cell count, 12,600/mL ever, minimal scarring and milia occasionally have (reference range, 4000–12,000/mL); platelet count, been reported (EBA-like phenotype).3 Erythematous 180,000/mL (reference range, 150,000–350,000/mL); annular plaques, urticarial papules, and targetoid erythrocyte sedimentation rate, 130 mm/h (reference lesions also have been described. In few cases, the range, 0–20 mm/h); serum creatinine, 0.7 mg/dL onset of vesicobullous lesions may coincide with (reference range, 0.3–0.7 mg/dL); urea nitrogen, exacerbation of SLE, particularly lupus nephritis and 21 mg/dL (reference range, 8–23 mg/dL); serum total cardiac vasculitis in 1 reported case.2,3,5 Two cases of protein, 5.5 g/dL (reference range, 6.0–8.0 g/dL); drug-induced BSLE to penicillamine and hydralazine albumin, 2.8 g/dL (reference range, 3.7–5.6 g/dL); and also have been reported.6,7 total globulin, 2.7 g/dL (reference range, 1.9–3.4 g/dL). Histopathology demonstrates a subepidermal Coagulation profile and liver function tests revealed bulla with neutrophilic-predominant inflammation no abnormalities. Urinalysis revealed presence of and neutrophilic dust, sometimes with papillary 18 CUTIS® WWW.CUTIS.COM Copyright Cutis 2012. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. WWW.CUTIS.COM Differential Diagnosis of Subepidermal Bullous Disorders in a Child Direct Target Response to Type Clinical Features Biopsy Immunofluorescence Antigen Treatment BSLE Urticated plaques, tense Subepidermal bulla, Granular/linear IgG, NC1 domain of Bullae respond bullae, nonscarring, fulfill papillary neutrophilic C3 1/2 IgA, IgM at BMZ type VII collagen rapidly to dapsone ARA criteria microabscesses (anchoring fibril, CUTIS 145 kD and 290 kD) EBA Tense vesicles, Subepidermal bulla, Linear IgG 1/2 C3, IgA, Type VII collagen Poor milia, scarring variable mixed infiltrate IgM at BMZ (anchoring fibril, 145 kD and Do Not Copy290 kD) CBDC Tense bullae; annular Subepidermal bulla, Linear IgA at BMZ BP180 Good response lesions; face, perineal, DH or BP-like (hemidesmosome), to dapsone or mucosal involvement LAD285 sulfapyridine BP Widespread tense Subepidermal bulla, Linear IgG, C3 1/2 IgM, BP230, BP180 Good response to bullae, urticated eosinophilic infiltrate IgA at BMZ (hemidesmosome) corticosteroids plaques Pediatric Dermatology VOLUME 89, JANUARY 2012 DH Pruritic papulovesicles; Subepidermal Granular IgA deposits at Epidermal Good response to symmetrical distribution; bulla, papillary tips of dermal papillae tissue dapsone, gluten- elbows, knees, buttocks neutrophilic transglutaminase free diet abscesses Abbreviations: BSLE, bullous systemic lupus erythematosus; ARA, American Rheumatism Association (Atlanta); BMZ, basement membrane zone; NC1, noncollagenous domain 1; EBA, epidermolysis bullosa acquisita; CBDC, chronic bullous disease of childhood; DH, dermatitis herpetiformis; BP, bullous pemphigoid; LAD, linear IgA disease. 19 Copyright Cutis 2012. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Pediatric Dermatology microabcesses resembling DH.1 Other features may SLE) causes tissue injury (in the DEJ), thereby expos- include leukocytoclastic vasculitis, basal cell vacu- ing previously sequestered antigenic epitopes (lam- olization, and presence of mucin. Direct immuno- inin 5 and other BMZ components) to autoreactive fluorescence shows deposition primarily of IgG, in