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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 41  |  Issue : 1  |  Page : 16-21

Childhood bullous systemic lupus erythematosus: unusual prognosis


Department of Dermatology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission09-Jan-2020
Date of Acceptance20-Mar-2020
Date of Web Publication23-Dec-2020

Correspondence Address:
Khaled Gharib
Department of Dermatology, Faculty of Medicine, Zagazig University, Zagazig 11516
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejdv.ejdv_2_20

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  Abstract 


Background Bullous systemic lupus erythematosus (BSLE) has rarely been described in pediatric lupus population, and the real prevalence of childhood-onset BSLE has not been reported. BSLE is a rare manifestation of systemic lupus erythematosus and is very rare in children. BSLE affects women more often than men, reflecting the female preponderance in systemic lupus erythematosus. It most often manifests in the second through fourth decades of life, but it has also been reported in children and older adults.
Patients and methods Herein, we describe a case of a 10-year-old female patient who presented with a 1-year history of recurrent itchy urticated skin eruption, which was followed 2 months later (after the first year) by a generalized blistering eruption with photosensitivity.
Results Histopathologic examination revealed a subepidermal blister and papillary-tip neutrophil microabscesses. Immunofluorescence studies showed linear immunoglobulin G (IgG) and IgC deposition along the BMZ with weaker staining of IgA and IgM. Laboratory tests revealed positive ANA, dsDNA, anti-SM antibodies, elevated erythrocyte sedimentation rate, and proteinuria.
Conclusion Although the course of BSLE is often remitting, but not in our case, treatment with dapsone is successful in most cases of BSLE.

Keywords: autoimmune bullous diseases, bullous systemic lupus, childhood


How to cite this article:
Gharib K. Childhood bullous systemic lupus erythematosus: unusual prognosis. Egypt J Dermatol Venerol 2021;41:16-21

How to cite this URL:
Gharib K. Childhood bullous systemic lupus erythematosus: unusual prognosis. Egypt J Dermatol Venerol [serial online] 2021 [cited 2022 Oct 1];41:16-21. Available from: http://www.ejdv.eg.net/text.asp?2021/41/1/16/304325


  Introduction Top


Bullous eruptions in patients with lupus erythematosus can be difficult to diagnose as bullous lesions can develop in lupus-specific lesions, and primary blistering disorders can also occur. Additionally, these patients tend to have multiple comorbidities, making them more likely to be on many medications that can lead to bullous drug reactions. A thorough history, clinical presentation, and histopathological findings along with direct immunofluorescence (DIF) can be helpful in diagnosing most cases [1],[2].

Bullous systemic lupus erythematosus (BSLE) has rarely been described in pediatric lupus population, and the real prevalence of childhood-onset BSLE has not been reported [3]. BSLE accounts for 2–3% of cases of autoimmune subepidermal blistering disease, with an estimated incidence of fewer than 0.5 cases per million populations per year [4],[5].

Blisters in systemic lupus erythematosus (SLE) can be owing to BSLE or SLE with blisters. Histologically, BSLE is a subepidermal blistering disease with an acute neutrophil-predominant infiltrate in the upper dermis. In contrast, the histology of cutaneous lesions of SLE with blistering reveals severe edema in the upper dermis and hydropic degeneration of the basal layer. Epidermal necrosis is seen at the advancing edges of the lesions [6].

The diagnosis of BSLE requires the following elements : fulfillment of the American College of Rheumatology criteria for SLE; an acquired vesiculobullous eruption; histologic evidence of a subepidermal blister and a predominantly neutrophilic dermal infiltrate; DIF microscopy demonstrating immunoglobulin G (IgG), with or without IgA and IgM deposits at the basement membrane zone; and evidence of antibodies to type VII collagen via DIF or indirect immunofluorescence on salt-split skin, immunoblotting, immunoprecipitation, enzyme-linked immunosorbent assay, or immunoelectron microscopy [7].

In the treatment of BSLE, dapsone is the effective basic therapy, and it often induces a dramatic response. In some cases, where an adequate response is not achieved with dapsone or the SLE disease activity index is high, other immunosuppressants, such as prednisolone, methotrexate, and azathioprine, can be used for controlling the eruption and suppressing the systemic symptoms. Moreover, in special case, where dapsone administration or other chemical drugs (MTX, azathioprine, etc.) induce serious adverse effects, biologic agents might be an alternative choice for BSLE [8].

Dapsone is the initial treatment of choice for BSLE. The response is usually dramatic, with cessation of new blister formation within 1–2 days and rapid healing of existing lesions. Low doses (25–50 mg/day) are often effective, although a higher dosage is sometimes required [8].

The course of BSLE is often remitting. The disorder frequently resolves spontaneously in less than 1 year. The development of BSLE in patients with SLE does not typically lead to increased mortality. Morbidity depends on the extent of the eruption and the response to therapy. In literature, no mortality had been done in the 15 cases of published BSLE. Herein, we present a bad prognosis that could happen in such cases.


  Case report Top


A 10-year-old girl patient presented with a 1-year history of recurrent itchy urticated skin eruption. Two months later, she started to develop blistering eruption with photosensitivity. On examination, there were urticated lesions in almost of the body, more on forearms, lower limbs (popliteal fossae), dorsum of hands, feet, palms, soles, groin, upper chest, and upper back, and tense bullae on urticated base and on normal skin; some bullae were arcuate, whereas others showed string of pearl configuration and oral erosions ([Figure 1] and [Figure 2]).
Figure 1 Vesicles before starting treatment.

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Figure 2 Clearance of vesicles after treatment.

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The histopathologic features of BSLE are a subepidermal vesicle and papillary-tip neutrophil microabscesses, indistinguishable from dermatitis herpetiform. Immunofluorescence shows linear IgG and IgC deposition along the BMZ, with weaker staining of IgA and IgM ([Figure 3] and [Figure 4]).
Figure 3 Subepidermal vesicle and papillary-tip neutrophil microabscesses.

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Figure 4 Linear IgG and IgC deposition along the BMZ with weaker staining of IgA and IgM. Ig, immunoglobulin.

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Detailed laboratory tests were done and revealed positive ANA (speckled type), dsDNA, and anti-SM antibodies (strong positive); elevated erythrocyte sedimentation rate (45 mm in the first hour, 82 mm in the second hour), hemoglobin (10.8 g/dl), and proteinuria (42.3 mg/dl, 634.5 mg/24 h); and normal serum creatinine, uric acid, and glucose. Based on the ARA criteria, our patient fulfilled the necessary criteria for the diagnosis of SLE, including photosensitivity, oral erosions, blood disorders, renal disorders, immunologic disorders, and elevated ANA. So, according to the diagnostic criteria proposed by ARA, the diagnosis of our case as BSLE was made.

The patient received systemic steroid (0.5 mg/kg/day), 15–20 mg for 2 weeks. However, new lesions appeared. After confirming the G6PD enzyme level, dapsone was added at a dose of 50 mg for 3 days, after which new lesions continued to appear. Steroid was increased to 25 mg/day=1 mg/kg/day with the same dose of dapsone. This combination resulted in marked improvement within 2 weeks of both signs and symptoms with improvement of skin lesions. Terbinafine (250 mg/day) was also given for treatment of tinea capitis. The patient revisited us after 6 months with active lesions. We started dapsone 50 mg tablet twice daily, but the patient was not controlled by this dose, so we decide to add steroids 30 mg/day.

The patient become more cachectic, refused eating, and hemoglobin was 5 mg/dl. The patient was administered 1000 ml of blood. However, no improvement revealed, so the patient was transferred to pediatric ICU. She received methylprednisolone (solumedrol 0.5/1 mg) 30 mg/kg/dose for three successive days and cyclophosphamide (endoxan 200 mg) 500 mg/m surface area every month. The investigations of renal function tests were normal, but the only finding was proteinuria; unfortunately, the patient developed pleural effusion and died.


  Discussion Top


In literature, only 20 cases have reported with BSLE in children until now, 15 girls and five boys, and then herein, we present the case number 21. Jacoby and Abraham published the first well-documented case of BSLE in 1979 of a 15-year-old male patient; in 1982, Hall and colleagues reported a 12-year-old male patient; in 1988, Kettler and colleagues reported an 8-year-old female patient; in 1995, Roholt and colleagues reported a 9-year-old female patient; in 1998, Shirhama and colleagues reported a 9-year-old female patient; in 1999, Chan and colleagues reported a 15-year-old female patient; in 2002, Nitta and colleagues reported a 17-year-old male patient; in 2003, Harris-Stith and colleagues reported a 17-year-old female patient; in 2005, Sirka and colleagues reported an 18-year-old female patient; in 2007, Vijayalakshmi and Jayavardhana reported BSLE and lupus nephritis in a 10-year-old boy; Kumar and Agarwal in 2007 reported a 13-year-old female patient; Saez-de-Ocariz and colleagues reported two cases of a 13-year-old and a 16-year-old female patient; Tincopa and colleagues reported a 13-year-old female patient; Rassbach and colleagues reported a 6-year-old female patient; Poojary and Rais reported BSLE and lupus nephritis in a 9-year-old girl; Lourence and colleagues reported three cases of two females and a male patient; and Christodoulou and colleagues reported a 16-year-old male patient ([Table 1]).
Table 1 Different cases published before

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The diagnosis of bullous eruptions in patients with lupus erythematosus (LE) can be difficult, as several different primary blistering disorders have been reported to occur in association with LE, including bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, epidermolysis bullosa acquisita, linear IgA, porphyria cutanea tarda, Stevens–Johnson syndrome, and toxic epidermal necrolysis [18]. These conditions must be differentiated from the bullous lesions that can occur in cutaneous lesions of LE, which can be owing to extensive vacuolar degeneration of the basement membrane or from antibodies to type VII collagen in BSLE. Patients with LE also tend to have multiple comorbidities, making them more likely to be on multiple medications, which can lead to bullous drug eruptions [19].

Blisters developing in patients with SLE raise two major differential diagnoses: BSLE and SLE with blisters. Lesions of SLE with blisters are polycyclic with an advancing blistering border. The lesions occur mainly on the face, neck, and upper arms, often on sun-exposed sites. The clinical appearances may mimic erythema multiforme and toxic epidermal necrolysis [19].

The relationship between lupus nephritis and BSLE does not appear to be casual. Type VII collagen, which is usually not present in normal glomeruli, is actively synthesized and incorporated in areas of glomerular and/or tubular scarring, irrespective of the underlying disease (including SLE nephritis). These findings confirm the de novo expression of fibrillary collagens in the diseased renal extracellular matrix [21].

It can be hypothesized that BSLE develops in patients with lupus nephritis once type VII collagen deposition has occurred in an abnormal location (e.g. the kidney) and antibody production toward this abnormally located protein has been initiated. Type VII collagen is the major component of anchoring fibrils at the dermal–epidermal junction and is the target of autoimmunity in patients with BSLE ([Table 2]) [20].
Table 2 Bullous systemic lupus erythematosus with nephritis

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  Conclusion Top


Although BSLE is extremely rare in children, it should be considered in the differential diagnosis for any child with vesiculobullous disease, and appropriate serologic testing for autoimmune markers and skin biopsy should be considered in these patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ranario JS, Smith JL. Bullous lesions in a patient with systemic lupus erythematosus. J Clin Aesthet Dermatol 2014; 7:44–49.  Back to cited text no. 1
    
2.
Vassileva S. Bullous systemic lupus erythematosus. Clin Dermatol 2004; 22:129–138.  Back to cited text no. 2
    
3.
Lourenço DM, Gomes RC, Aikawa NE, Campos LM, Romiti R, Silva CA. Childhood-onset bullous systemic lupus erythematosus. Lupus 2014; 23:1422–1425.  Back to cited text no. 3
    
4.
Contestable JJ, Edhegard KD, Meyerle JH. Bullous systemic lupus erythematosus: a review and update to diagnosis and treatment. Am J Clin Dermatol 2014; 15:517–524.  Back to cited text no. 4
    
5.
Tincopa M, Puttgen KB, Sule S, Cohen BA, Gerstenblith MR. Bullous lupus: an unusual initial presentation of systemic lupus erythematosus in an adolescent girl. Pediatr Dermatol 2010; 27:373–376.  Back to cited text no. 5
    
6.
Vijayalakshmi AM, Jayavardhana A. Bullous systemic lupus erythematosus and lupus nephritis in a 10-year-old boy. Indian Pediatr 2007; 44:861–863.  Back to cited text no. 6
    
7.
Kumar S, Agarwal I. Unusual presentation of childhood systemic lupus erythematosus. Pediatr Rheumatol 2007; 5:20.  Back to cited text no. 7
    
8.
Christodoulou G, Powell M, Nguyen VH, Watters K, Jafarian F. An atypical case of bullous systemic lupus erythematosus in a 16-year-old boy. Pediatr Dermatol 2014; 31:e164–e166. Christodoulou G , Powell M , Nguyen VH , Watters K , Jafarian F . An atypical case of bullous systemic lupus erythematosus in a 16-year-old boy. Pediatr Dermatol 2014; 31:e164–e166.  Back to cited text no. 8
    
9.
Jacoby RA, Abraham AA. Bullous dermatosis and systemic lupus erythematosus in a 15-year-old-boy. Arch Dermatol 1979; 115:1094–1097.  Back to cited text no. 9
    
10.
Hall RP, Lawley TJ, Smith HR, Katz SI. Bullous eruption of systemic lupus erythematosus.Dramatic response to dapsone therapy. Ann Intern Med 1982; 197:165–170.  Back to cited text no. 10
    
11.
Kettler AH, Bean SF, Duffy JO, Gammon WR. Systemic lupus erythematosus presenting as a bullous eruption in a child. Arch Dermatol 1988; 124:1083–1087.  Back to cited text no. 11
    
12.
Roholt NS, Lapiere JC, Wang JI, Bernstein LJ, Woodley DT, Eramo LR. Localized linear bullous eruption of systemic lupus erythematosus in a child. Pediatr Dermatol 1995; 12:138–144.  Back to cited text no. 12
    
13.
Shirhama S, Furukawa F, Yagi H, Tanaka T, Hashimoto T, Takigawa M. Bullous systemic lupus erythematosus: detection of antibodies against noncollagenous domain of type VII collagen. J Am Acad Dermatol 1998; 38:844–848.  Back to cited text no. 13
    
14.
Chan LS, Lapier JC, Chen M, Traczyk T, Mancini AJ, Paller AS et al. Bullous systemic lupus erythematosus with autoantibodies recognizing multiple skin basement membrane components, bullous pemphigoid antigen 1, laminin-5, laminin-6, and type VII collagen. Arch Dermatol 1999; 135:569–573.  Back to cited text no. 14
    
15.
Nitta Y, Kawamwa C, Hashimoto T. Vesicullobullous systemic lupus erythematosus: a case with circulating IgG and IgA autoantibodies to type VII collagen. J Am Acad Dermatol 2002; 47(5 Suppl):283–286.  Back to cited text no. 15
    
16.
Harris-Stith R, Ericsson QL, Elston DM, David-Bajar K. Bullous eruption: a manifestation of lupus erythematosus. Cutis 2003; 72:31–37.  Back to cited text no. 16
    
17.
Sirka CS, Padhi T, Mohanty P, Patel DK, Parida PR, Kar CR. Bullous systemic lupus erythematosus: response to dapsone in two patients. Indian J Dermatol Venereol Leprol 2005; 71:54–56.  Back to cited text no. 17
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18.
Sáez-de-Ocariz M, Espinosa-Rosales F, López-Corella E, de León-Bojorge B. Bullous lesions as a manifestation of systemic lupus erythematosus in two Mexican teenagers. Pediatr Rheumatol 2010; 8:19.  Back to cited text no. 18
    
19.
Rassbach C, Shah N, Davis A. A 6-year-old girl with extensive bullous skin lesions. Pediatr Ann 2012; 41:229–231.  Back to cited text no. 19
    
20.
Poojary S, Rais S. Bullous systemic lupus erythematosus with lupus nephritis: a rare case of a subepidermal bullous disorder in a child. Cutis 2012; 89:17–21.  Back to cited text no. 20
    
21.
Fujimoto W, Hamada T, Yamada J, Matsuura H, Iwatsuki K. Bullous systemic lupus erythematosus as an initial manifestation of SLE. J Dermatol 2005; 32:1021–1027.  Back to cited text no. 21
    


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