Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Bullous Systemic Lupus Erythematosus (BSLE) Workup

  • Author: Hillary D Johnson-Jahangir, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Dec 15, 2015
 

Approach Considerations

Bullous systemic lupus erythematosus occurs in the setting of systemic lupus erythematosus; thus, ANA test results generally are positive. Anti-dsDNA, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, and anticardiolipin antibodies may also be detected.

Other laboratory abnormalities related to systemic lupus erythematosus can include low levels of complement (ie, C3, C4, CH50), anemia, leukopenia, thrombocytopenia, proteinuria or cellular casts upon urinalysis, and an elevated erythrocyte sedimentation rate. (See also Systemic Lupus Erythematosus and Lupus Nephritis.)

Laboratory findings in persons with toxic epidermal necrolysis–like lupus erythematosus vary depending on the underlying type of lupus erythematosus present.

Although the lupus erythematosus patients with erythema multiforme–like skin lesions who were originally described by Rowell and colleagues had immunologic features that included a speckled pattern of ANAs, anti-Ro/SS-A and/or La/SS-B antibodies, and a positive rheumatoid factor, these findings are not consistently observed in lupus erythematosus patients with this clinical presentation. Anticardiolipin antibodies and lupus anticoagulant have also been reported in individuals with Rowell syndrome.

Procedures

Diagnosis of bullous systemic lupus erythematosus requires skin biopsy specimens for routine light microscopy (preferably from the edge of a fresh blister, including adjacent, clinically unblistered skin) and DIF microscopy (from perilesional skin).

Next

Histologic Findings

Light microscopy

Histologically, bullous systemic lupus erythematosus is characterized by dermoepidermal separation beneath an intact epidermis. A predominantly neutrophilic infiltrate is observed in an edematous upper dermis, either concentrated in the dermal papillae (similar to dermatitis herpetiformis) or distributed in a continuous band beneath the BMZ (similar to linear IgA bullous dermatosis).

Nuclear dust is often apparent, and a variable number of eosinophils and mononuclear cells are present within the dermal infiltrate. Basal keratinocyte vacuolization and other histologic features of cutaneous lupus erythematosus are typically absent.

Immunofluorescence microscopy

DIF microscopy of perilesional skin reveals deposition of IgG (with and without IgM and IgA) and complement in a linear or granular bandlike pattern at the BMZ.

In type 1 bullous systemic lupus erythematosus, DIF of salt-split perilesional skin and/or IIF microscopy following incubation of the patient's serum with salt-split normal human skin reveals immunoglobulin deposits localized to the dermal floor of the split.[27] Immunoblot and immunoprecipitation studies using the patient's serum can confirm that these antibodies recognize the 290- and 145-kd proteins of type VII collagen. An enzyme-linked immunosorbent assay (ELISA) test for rapid detection of anti–type VII collagen NC1 domain antibodies has also been developed.

In addition, direct immunoelectron microscopy can be used to demonstrate that the immunoglobulin deposits are codistributed with anchoring fibrils/type VII collagen within and just below the lamina densa.

Cases with negative IIF and an undetermined sublocalization of anti-BMZ antibodies (or antibodies recognizing a dermal antigen other than collagen VII) are referred to as type 2 bullous systemic lupus erythematosus. Of note, circulating antibodies to type VII collagen are less likely to be present in patients with a granular pattern of fluorescence on DIF. Bullous systemic lupus erythematosus characterized by immunoglobulin binding the epidermal roof (type 3 bullous systemic lupus erythematosus) or the roof and the dermal floor of salt-split skin has also been observed. Antigens in such patients have included bullous pemphigoid antigen 1, laminin-5, and laminin-6.

Histologic findings in toxic epidermal necrolysis–like and erythema multiforme–like lupus erythematosus lesions

The histologic features of toxic epidermal necrolysis–like lupus erythematosus consist of full-thickness epidermal necrosis and a sparse lymphocytic infiltrate in the upper dermis, as are seen in drug-induced toxic epidermal necrolysis.

Rowell syndrome is characterized by a vacuolar interface dermatitis with lymphocyte exocytosis; prominent necrotic keratinocytes in all layers of the epidermis; a mild, superficial, perivascular lymphocytic infiltrate; and dermal edema, features suggestive of erythema multiforme but also compatible with early, hyperacute cutaneous lupus erythematosus. DIF findings are usually negative.

Previous
 
 
Contributor Information and Disclosures
Author

Hillary D Johnson-Jahangir, MD, PhD Clinical Assistant Professor, Department of Dermatology, University of Iowa, Roy J and Lucille A Carver College of Medicine

Hillary D Johnson-Jahangir, MD, PhD is a member of the following medical societies: American College of Mohs Surgery, American Medical Association, American Society for Dermatologic Surgery, American Society for Laser Medicine and Surgery, Iowa Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Alice L Ye Medical Student, University of Iowa, Carver College of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Julie V Schaffer, MD Assistant Professor of Dermatology and Pediatrics, Director of Dermatology Resident Education, Director of Pediatric Dermatology Unit, New York University School of Medicine

Disclosure: Nothing to disclose.

Ivan D Camacho, MD Dermatologist, Private Practice; Voluntary Assistant Professor of Dermatology, Department of Dermatology and Cutaneous Surgery, University of Miami, Leonard M Miller School of Medicine

Ivan D Camacho, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Florida Medical Association, International Society of Dermatology, Women's Dermatologic Society

Disclosure: Nothing to disclose.

Acknowledgements

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Consulting fee Consulting; Celgene Honoraria Safety Monitoring Committee; GSK - Glaxo Smith Kline Consulting fee Consulting; TenXBioPharma Consulting fee Safety Monitoring Committee

Michael Girardi, MD Associate Professor and Residency Director, Department of Dermatology, Yale University School of Medicine

Michael Girardi, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Michael J Wells, MD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

References
  1. Fujimoto W, Hamada T, Yamada J, Matsuura H, Iwatsuki K. Bullous Systemic Lupus Erythematosus as an Initial Manifestation of SLE. J Dermatol. 2005 Dec. 32(12):1021-7. [Medline].

  2. Poojary S, Rais S. Bullous systemic lupus erythematosus with lupus nephritis: a rare case of a subepidermal bullous disorder in a child. Cutis. 2012 Jan. 89(1):17-21. [Medline].

  3. Daneshpazhooh M, Shahdi M, Aghaeepoor M, Hasiri G, Chams C. A comparative study of antibody titers of blister fluid and serum in patients with subepidermal immunobullous diseases. Int J Dermatol. 2004 May. 43(5):348-51. [Medline].

  4. Roustan G, Salas C, Barbadillo C, Sánchez Yus E, Mulero J, Simón A. Lupus erythematosus with an erythema multiforme-like eruption. Eur J Dermatol. 2000 Aug. 10(6):459-62. [Medline].

  5. Horne NS, Narayan AR, Young RM, Frieri M. Toxic epidermal necrolysis in systemic lupus erythematosus. Autoimmun Rev. 2006 Feb. 5(2):160-4. [Medline].

  6. Mandelcorn R, Shear NH. Lupus-associated toxic epidermal necrolysis: a novel manifestation of lupus?. J Am Acad Dermatol. 2003 Apr. 48(4):525-9. [Medline].

  7. Paradela S, Martinez-Gomez W, Fernandez-Jorge B, et al. Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus. Lupus. 2007. 16(9):741-5. [Medline].

  8. Yang S, Gao Y, Song Y, Liu J, Yang C, Liu J, et al. The study of the participation of basement membrane zone antibodies in the formation of the lupus band in systemic lupus erythematosus. Int J Dermatol. 2004 Jun. 43(6):420-7. [Medline].

  9. Grabell DA, Matthews LA, Yancey KB, Chong BF. Detection of Type VII Collagen Autoantibodies Before the Onset of Bullous Systemic Lupus Erythematosus. JAMA Dermatol. 2015 May. 151 (5):539-43. [Medline]. [Full Text].

  10. Ishii N, Yoshida M, Hisamatsu Y, et al. Epidermolysis bullosa acquisita sera react with distinct epitopes on the NC1 and NC2 domains of type VII collagen: study using immunoblotting of domain-specific recombinant proteins and postembedding immunoelectron microscopy. Br J Dermatol. 2004 May. 150(5):843-51. [Medline].

  11. Chen M, Doostan A, Bandyopadhyay P, et al. The cartilage matrix protein subdomain of type VII collagen is pathogenic for epidermolysis bullosa acquisita. Am J Pathol. 2007 Jun. 170(6):2009-18. [Medline]. [Full Text].

  12. Woodley DT, Ram R, Doostan A, et al. Induction of epidermolysis bullosa acquisita in mice by passive transfer of autoantibodies from patients. J Invest Dermatol. 2006 Jun. 126(6):1323-30. [Medline].

  13. Chen L, Peterson JD, Zheng WY, Lin SX, Chan LS. Autoimmunity to type VII collagen in SKH1 mice is independent of regulatory T cells. Clin Exp Immunol. 2006 Aug. 145(2):322-31. [Medline]. [Full Text].

  14. Chan LS, Lapiere JC, Chen M, 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 May. 135(5):569-73. [Medline].

  15. Chen M, Chan LS, Cai X, et al. Development of an ELISA for rapid detection of anti-type VII collagen autoantibodies in epidermolysis bullosa acquisita. J Invest Dermatol. 1997 Jan. 108(1):68-72. [Medline].

  16. Fujii K, Fujimoto W, Ueda M, Makino E, Arata J. Detection of anti-type VII collagen antibody in Sjögren's syndrome/lupus erythematosus overlap syndrome with transient bullous systemic lupus erythematosus. Br J Dermatol. 1998 Aug. 139(2):302-6. [Medline].

  17. Hertl M, Eming R, Veldman C. T cell control in autoimmune bullous skin disorders. J Clin Invest. 2006 May. 116(5):1159-66. [Medline]. [Full Text].

  18. Ting W, Stone MS, Racila D, Scofield RH, Sontheimer RD. Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus and the spectrum of the acute syndrome of apoptotic pan-epidermolysis (ASAP): a case report, concept review and proposal for new classification of lupus erythematosus vesiculobullous skin lesions. Lupus. 2004. 13(12):941-50. [Medline].

  19. Nasongkhla P, Pratchyapruit W, Tagami H. Bullous systemic lupus erythematosus induced by UVB: report a case. J Med Assoc Thai. 2012 Jul. 95(7):969-73. [Medline].

  20. Lourenço DM, Gomes RC, Aikawa NE, Campos LM, Romiti R, Silva CA. Childhood-onset bullous systemic lupus erythematosus. Lupus. 2014 Nov. 23 (13):1422-5. [Medline].

  21. Yogarajah M, Sivasambu B, Jaffe EA. Bullous systemic lupus erythematosus associated with esophagitis dissecans superficialis. Case Rep Rheumatol. 2015. 2015:930683. [Medline]. [Full Text].

  22. Khandpur S, Das S, Singh MK. Rowell's syndrome revisited: report of two cases from India. Int J Dermatol. 2005 Jul. 44(7):545-9. [Medline].

  23. Pandhi D, Singal A, Agarwal P. Rowell's syndrome and associated antiphospholipid syndrome. Clin Exp Dermatol. 2004 Jan. 29(1):22-4. [Medline].

  24. Shteyngarts AR, Warner MR, Camisa C. Lupus erythematosus associated with erythema multiforme: does Rowell's syndrome exist?. J Am Acad Dermatol. 1999 May. 40(5 Pt 1):773-7. [Medline].

  25. Zeitouni NC, Funaro D, Cloutier RA, Gagné E, Claveau J. Redefining Rowell's syndrome. Br J Dermatol. 2000 Feb. 142(2):343-6. [Medline].

  26. Paradela S, Martínez-Gómez W, Fernández-Jorge B, et al. Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus. Lupus. 2007. 16(9):741-5. [Medline].

  27. Gammon WR, Fine JD, Forbes M, Briggaman RA. Immunofluorescence on split skin for the detection and differentiation of basement membrane zone autoantibodies. J Am Acad Dermatol. 1992 Jul. 27(1):79-87. [Medline].

  28. Malcangi G, Brandozzi G, Giangiacomi M, Zampetti M, Danieli MG. Bullous SLE: response to methotrexate and relationship with disease activity. Lupus. 2003. 12(1):63-6. [Medline].

  29. Alsanafi S, Kovarik C, Mermelstein AL, Werth VP. Rituximab in the treatment of bullous systemic lupus erythematosus. J Clin Rheumatol. 2011 Apr. 17(3):142-4. [Medline].

  30. Hamminga EA, Vermeer MH. Bullous systemic lupus erythematosus responding to mycophenolate mofetil. Eur J Dermatol. 2010 Nov-Dec. 20(6):844-5. [Medline].

  31. Anyanwu CO, Ang CC, Werth VP. Oral mucosal involvement in bullous lupus. Arthritis Rheum. 2013 Oct. 65 (10):2622. [Medline].

 
Previous
Next
 
Tense vesiculobullous lesions on the neck of a patient with bullous systemic lupus erythematosus.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.