AN ATYPICAL PRESENTATION OF BULLOUS SYSTEMIC ERYTHEMATOSUS Robert Murgia, DO; Daniel Hurd, DO Introduction: LewisGale Hospital Montgomery, Blacksburg, VA Bullous systemic (BSLE) is a particularly uncommon manifestation of Histopathologically, BSLE presents with subepidermal vesicles and neutrophilic microabscesses nonscarring subepidermal bullous eruption of systemic lupus erythematosus (SLE) with an in the papillary tips, making it difficult to distinguish from DH.12 In many cases, may incidence of 0.26 per million persons per year in adults.1,2 BSLE presents with rapid onset of not be solely confined to the papillae, but also form a continuous band concentrated in the upper vesicles or bullae distributed throughout the body, concentrated on the face, neck, , both below and on the zone (BMZ) as well as in the cavity. extremities, and trunk.2,3 The simultaneous occurrence of a primary bullous in a In some cases, histologic features of necrotizing , including leukocytoclasis, erythrocyte patient with SLE must be differentiated from BSLE, as bullous (BP), extravasation, and of blood vessels, may be evident, which are rarely seen in DH. herpetiformis (DH), linear IgA dermatosis, and acquisita (EBA) have Classic features of primary lupus , such as epidermal atrophy, basal all been reported in association with SLE.4,5 Typically, patients with BSLE will meet criteria vacuolization, and thickening of the BMZ, are typically absent in bullous lesions.8,11 Direct for SLE as defined by the American College of (ACR) in addition to a (DIF) studies show deposits of IgG, C3, IgA, and IgM at the BMZ in two widespread vesiculobullous eruption that is commonly unrelated to the severity of the SLE.6 types of patterns, linear and granular, with an occasional mixed granular-linear configuration. BSLE is a rare and often difficult to diagnose manifestation of SLE, especially when it is the Indirect immunofluorescence with salt-split demonstrates immunoglobulin deposition on the initial presentation.3 Here we report such a case of a 57-year-old, Caucasian male with dermal side of the split.13 BSLE. The criteria for the diagnosis of BSLE proposed by Camisa and Sharma include a diagnosis of Case Report: SLE based on the criteria of the ACR, vesicles and bullae located on but not limited to sun- A 57-year-old, Caucasian male presented with a 1-month history of a diffuse exposed skin; histopathologic findings similar to DH; and deposition of IgG and/or IgM and often vesiculobullous, pruritic, and painful eruption. He admitted to an abrupt onset of lesions. His IgA at the BMZ by DIF. BSLE has been further classified into two distinct subtypes by Gammon medical history was significant for stage IV chronic secondary to focal and Briggaman: patients with circulating to type VII are designated as cases segmental (FSGS), of chronic disease, and of BSLE-1 while patients designated as cases of BSLE-2 do not have these antibodies. 4,6,14 hyperparathyroidism. Physical examination revealed innumerable tense bullae on his trunk Clinically, it is not possible to distinguish between the two types of BSLE.9 as well as upper and lower extremities bilaterally, with sparing of both knees and elbows. (Figures 1-2) Skin fragility and apparent scarring were absent. Upon oral examination, multiple erosions were observed. of BSLE (Table 1) includes EBA, BP, DH, and linear IgA dermatosis, which can be distinguished on the basis of clinical, histopathologic, and immunologic findings.1 Unlike FIGURE 1: Diffuse vesicles and bullae FIGURE 2: Large bullae on left leg with patients with EBA, most patients with BSLE respond dramatically to dapsone.8 The A biopsy specimen of perilesional skin demonstrated -rich subepidermal bullae covering abdomen. background of erythematous macules and vesiculobullous eruptions of BSLE can remain for weeks or months, but typically show rapid with clumps of neutrophils filling the dermal papillae and lining up along the dermal- plaques. improvement and resolution with oral dapsone, at 50-100mg/day.2,6,10,11 Blister clearance usually epidermal junction (DEJ) with strong discontinuous IgG and C3 lining the basement begins within 48 hours of beginning treatment and the eruptions are cleared within one week, membrane zone (Figure 3). often using lower doses of dapsone (25-50mg).9,11 Unfortunately, most patients will develop a 1- to 2-g drop in hemoglobin levels after treatment with dapsone, which prompted initiation of a Routine laboratory investigations revealed the following results: hemoglobin, 8.6 g/dL lower than typical therapeutic dose at 25mg/day due to our patient’s consistent hemoglobin level (reference range, 13.0– 16.0 g/dL); total count, 5,200/mL (reference range, of 8.6g/dL.15 In patients who do not respond to dapsone or in whom dapsone is contraindicated, 4000–10,500/mL); platelet count, 487,000/mL (reference range, 130,000–400,000/mL); other therapeutic options such as , , , colchicine, and serum creatinine, 3.06 mg/dL (reference range, 0.5–1.4 mg/dL); urea nitrogen, 59 mg/dL antimalarials have been reported to be useful.1,6 (reference range, 6–20 mg/dL); serum total , 6.8 g/dL (reference range, 6.0–8.3 g/dL); albumin, 4.3 g/dL (reference range, 3.2–5.5 g/dL); and total globulin, 2.5 g/dL The in patients with SLE and bullous lesions is determined largely by the visceral (reference range, 1.7–3.9 g/dL). A urinalysis revealed a urine protein value of 100mg/DL manifestations of the SLE. The activity of the systemic and skin disease is generally unrelated, (reference, 0). revealed no abnormalities. Additional investigation however.6,14 Our patient fulfilled criteria for BSLE, but further classification of type 1 or type 2 revealed an antinuclear of 1:40 with a positive indirect fluorescent antibody as well BSLE was not made, as testing for antibodies to type VII collagen were unable to be performed as an elevated anti-dsDNA at 32 (reference range, ≤ 4). Smith antigen and Sjögren in this patient. Although rare, BSLE should be considered in the differential diagnosis of a syndrome A and B antigens were negative. Tests for antibodies to type VII collagen were not subepidermal blistering disease, even if no prior diagnosis of SLE has been made. As seen with able to be performed. our patient, bullous eruptions may be the initial manifestation.

FIGURE 3: Subepidermal inflammatory blister with consistent presence A glucose-6-phosphate dehydrogenase level was found to be unremarkable and treatment References with dapsone 25mg PO daily was initiated due to his longstanding history of anemia. There of papillary dermal showing diffuse collections of neutrophils was no improvement noted after a 2-week period. He was then switched to a regimen of and nuclear dust in the upper dermis. •Poojary S, Rais S: Bullous Systemic Lupus Erythematosus With Lupus : A Rare Case of a Subepidermal Bullous Disorder in a oral tapered over 3 weeks before starting 200mg PO twice Child. Cutis 2012;89: 17-21 •Vijayalakshami A, Jayavardhana A: Bullous Systemic Lupus Erythematosus and in a 10-year-old Boy. Indian Pediatrics daily. A dramatic resolution of bullous lesions was observed within 2 weeks and he admits to Differential Diagnosis of Subepidermal Bullous Eruption 2007;44(11): 861-863 continued clearance of all lesions. •Coo E, Belisario M, Cauilan M: Bullous systemic lupus erythematosus presenting initially as a vesiculobullous eruption without overt manifestations of SLE. J Am Acad Dermatol 2017;AB59: 5517 •Camisa C, Sharma H Vesiculobullous systemic lupus erythematosus. J Am Acad Dermatol 1983;9: 924-933 Discussion Type Clinical Features Histological Features Direct Immunofluorescence Target Antigen •Ranario J, Smith J: Bullous Lesions in a Patient with Systemic Lupus Erythematosus. J Clin Aesthet Dermatol 2014;7(9): 44-49 BSLE is believed to be triggered by circulating to type VII collagen. This •Harris-Stith R, Erickson Q, Elston D, David-Bajar K: Bullous Eruption: A Manifestation of Lupus Erythematosus. Cutis 2003;72: 31-37 eruption may represent the concurrence of lupus with an autoimmune blistering disease due •Bolognia JL, Jorizzo JL, Schaffer JV. . 3rd ed. Philadelphia: Elsevier Saunders; 2012. 623p 7 Bullous Systemic Lupus Erythematosis Tense, nonscarring bullae and Subepidermal bullae with Linear/granular IgG, C3 +/- IgA and IgM at BMZ Type VII Collagen •Gammon W, Briggaman R: Bullous SLE: A phenotypically distinctive but immunologically heterogeneous bullous disorder. J Invest to the autoantibodies to a component of the basement membrane zone. Most patients have SLE neutrophils infiltrating papillary Dermatol 1993;100: 28S-34S 8 dermis been young, black women, but all ages, races, and both sexes are affected. •Sebaratnam D, Murrell D: Bullous Systemic Lupus Erythematosus. Dermatol Clin 2011;29: 649-653 •Fujimoto W,Hamada T, Yamada J, Matsuura H et al.: Bullous Systemic Lupus Erythematosus as an Initial Manifestation of SLE. The Epidermolysis Bullosa Acquisita Tense, scarring bullae with fragile Subepidermal bullae with Linear IgG +/- C3, IgA, and IgM at BMZ Type VII Collagen skin in trauamatized areas variable infiltrate Journal of Dermatology 2005;32: 1021-1027 The clinical presentation of BSLE is generally that of an acutely generalized vesicobullous •Hall R, Lawley T, Smith H, Katz S: Bullous eruption of systemic lupus erythematosus. Dramatic response to dapsone therapy. Ann Intern eruption in patients who meet the American Association revised criteria for Med 1982;97: 165-170 •Vassileva S. Bullous systemic lupus erythematosus. Clin Dermatol. 2004;22:129-138 SLE.9 Lesions may involve flexural or extensor skin and mucosal surfaces of the mouth and Widespread urticarial lesions Subepidermal bullae with Linear IgG, C3 +/- IgA and IgM at BMZ BPAG230 forming tense bullae eosinophilic infiltrate BPAG180 •Weinberg MA, Insler MS, Campen RB, Mucocutaneous features of autoimmune blistering . Oral Surg Oral Med Oral Pathol Oral pharynx. may form on erythematous skin and may be preceded by erythematous Radio Endod. 1997; 84: 517-534 macules and plaques. Lesions may be large and tense and resemble those of BP, or small Pruritic grouped vesicles Subepidermal bullae with Granular deposits of IgA within dermal papillae Epidermal tissue transglutaminase •Gammon WR, Briggaman RA. Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus diseases of to symmetrically distributed over neutrophils infiltrating papillary type VII collagen. Dermatol Clin. 1993;11:535-547 and grouped and resemble those of DH. BSLE does not exhibit mechanical fragility of the elbows, knees, and buttocks dermis skin with tense bullae that subsequently heal with scars and milia contrasting with EBA. •Gleid M, Rico J. Treatment of autoimmune blistering diseases. Dermatol Clin. 1999;17:431-440 Patients may complain of itching, which may sometimes be severe. However, pruritus is not prominent. Additionally, the primary lesions seen in both SLE and discoid lupus are not 8 Linear IgA dermatosis Grouped bullae over extensor Subepidermal bullae with Linear IgA +/- C3 at BMZ LAD-1 commonly associated with BSLE. There are conflicting reports that BSLE bullous eruptions surfaces and buttocks neutrophils infiltrating papillary LACD97 coincide with other systemic manifestations of SLE. Certain studies report that BSLE clinical dermis signs have no relationship with SLE flares and that BSLE can be the initial manifestation of SLE.2,10,11 Table 1. Differential Diagnosis of Subepidermal Bullous Eruption