Brand-Ad-30-6
 IADVL
Indexed with PubMed and Science Citation Index (E) 
 
Users online: 299 
     Home | Feedback | Login 
About Current Issue Archive Ahead of print Search Instructions Online Submission Subscribe What's New Contact  
  Navigate here 
  Search
 
  
 Resource links
   Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
   Article in PDF (1,825 KB)
   Citation Manager
   Access Statistics
   Reader Comments
   Email Alert *
   Add to My List *
* Registration required (free)  

 
  In this article
   References
   Article Figures

 Article Access Statistics
    Viewed2627    
    Printed39    
    Emailed0    
    PDF Downloaded63    
    Comments [Add]    
    Cited by others 1    

Recommend this journal

 


 
 Table of Contents    
LETTER TO EDITOR
Year : 2013  |  Volume : 79  |  Issue : 5  |  Page : 719-720

Acquired bullous dermatosis associated with IgA multiple myeloma


1 Department of Pathology, AP-HP H˘pital, Saint Louis; UniversitÚ Paris 7 Denis Diderot, Paris, France
2 Department of Dermatology, AP-HP H˘pital, Saint Louis; UniversitÚ Paris 7 Denis Diderot, Paris, France
3 Department of Dermatology, AP-HP H˘pital, Saint Louis, France
4 Department of Immunohaematology, AP-HP H˘pital, Saint Louis, France

Date of Web Publication21-Aug-2013

Correspondence Address:
Maxime Battistella
Department of Pathology, APHP H˘pital Saint Louis, Paris - 75010
France
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0378-6323.116753

Rights and Permissions



How to cite this article:
Battistella M, Hickman G, Petit A, Asli B, Bouaziz JD, Janin A, Bagot M. Acquired bullous dermatosis associated with IgA multiple myeloma. Indian J Dermatol Venereol Leprol 2013;79:719-20

How to cite this URL:
Battistella M, Hickman G, Petit A, Asli B, Bouaziz JD, Janin A, Bagot M. Acquired bullous dermatosis associated with IgA multiple myeloma. Indian J Dermatol Venereol Leprol [serial online] 2013 [cited 2020 Dec 6];79:719-20. Available from: https://www.ijdvl.com/text.asp?2013/79/5/719/116753


Sir,

Several skin disorders have been described in patients with monoclonal gammapathies. [1] Only two cases of acquired bullous dermatosis associated with immunoglobulin A (IgA) multiple myeloma have been reported in the literature, for which no target antigen has been identified.

We report the association of IgA λ multiple myeloma with cutaneous vasculitis and bullous dermatosis characterized by subepidermal deposits of IgA λ specific for a 120 kDa epidermal antigen. An 87-year-old woman developed in 2007, a pruriginous bullous eruption on the legs, trunk, hands, face, and scalp, with no mucosal involvement. The skin biopsy showed a subepidermal blister associated with an infiltrate of neutrophils and eosinophils. Immunoblot analysis on epidermal extracts detected several IgA bands. Serum immunoelectrophoresis revealed IgA λ paraprotein (30.2 g/L) and bone marrow aspiration showed 37% of atypical plasma cells. Magnetic resonance imaging of the rachis found several lytic lesions of the vertebrae. Stage III IgA multiple myeloma was diagnosed and treated with melphalan, prednisone, and thalidomide for 6 months. Complete remission was achieved after three cycles, with rapid resolution of the skin lesions. After 32 months of remission, in May 2010, a relapse of bullous skin lesions was observed on the abdomen, face, and limbs [Figure 1], whereas serum immunoelectrophoresis was normal. Palpable purpura without bullae was present on the legs. A skin biopsy on the abdomen showed a subepidermal blister with upper dermal neutrophilic infiltrate and leukocytoclastic vasculitis of the small vessels [Figure 2]. Direct immunofluorescence (DIF) revealed thick subepidermal deposits of IgA λ, and no IgG, IgA, or C3 deposits in the vessel wall [Figure 3]. Treatment with dapsone 100 mg/day and topical steroids during 5 months was ineffective. In September 2010, a 36.7 g/L seric IgA λ paraprotein was detected. Immunoblot on normal epidermal extracts detected a 120 kDa target with IgA. Indirect immunofluorescence on monkey and rat esophagus was negative, as well as BP180 enzyme-linked immunosorbent assay. The patient was started on cyclophosphamide (500 mg oral weekly), prednisone (100 mg oral each other day), and thalidomide (50 mg oral daily). Skin lesions initially healed but the tolerance of the chemotherapy was bad, and the patient ultimately died of severe systemic infection.
Figure 1: Round or annular bullous and erosive cutaneous lesions on the abdomen

Click here to view
Figure 2: Subepidermal blister with numerous neutrophils in the papillary dermis. Inset: Dermal vasculitis with fibrinoid necrosis and neutrophil infiltrate (H and E; ×200, inset: ×400)

Click here to view
Figure 3: Direct immunofluorescence with fl uorescein isothiocyanateconjugated anti-IgA antibody showing thick subepidermal deposits (immunofluorescence staining, ×200)

Click here to view


Multiple myeloma has been associated with a variety of specific and nonspecific skin manifestations. [1] Multiple myeloma, and especially IgA-myeloma, has been associated with neutrophilic dermatoses, that is, Sweet's syndrome, pyoderma gangrenosum, erythema elevatum diutinum, eccrine neutrophilic hidradenitis, and Sneddon-Wilkinson subcorneal pustulosis. IgA pemphigus and Henoch-Schönlein purpura (IgA-mediated leukocytoclastic vasculitis) have also been reported in association with IgA-myeloma.

In this case, a peculiar IgA-mediated acquired bullous eruption revealed IgA multiple myeloma, and the recurrence of the skin lesions predicted the relapse of the myeloma. The recurrence of the bullous lesions was associated with leukocytoclastic vasculitis. The vasculitis may have been secondary to intense neutrophils infiltration as is seen in some cases of Sweet's syndrome. Bullous lesions in the context of cancer may have risen hypotheses such as bullous Sweet syndrome or paraneoplastic pemphigus that have been ruled out by DIF and histopathology.

Only two other cases of acquired bullous dermatosis associated with IgA multiple myeloma have been reported in the literature. [2],[3] The three cases shared some features: The eruption appeared before the diagnosis of paraproteinemia; the skin biopsy showed subepidermal bullae with a predominantly neutrophilic infiltrate; and DIF showed thick subepidermal IgA deposits in the upper dermis.

Acquired bullous disorders with other paraproteins than IgA have been reported, in association with IgG multiple myeloma, or with IgM gammopathy. [4] Bullous lesions are supposed to be induced by the monoclonal paraproteins, acting as autoantibodies. We report for the first time a 120 kDa epidermal protein as the specific target of the IgA paraprotein. This protein probably corresponds to the 120 kDa linear IgA dermatosis antigen (LAD-1), an autoantigen target in linear IgA bullous dermatosis (LAD). [5] The subepidermal blister with neutrophils accumulating in the papillary dermis in our case was reminiscent of LAD. However, DIF was peculiar, with thick IgA λ deposits in the papillary dermis, suggesting a specific paraneoplastic blistering disease due to IgA paraprotein and not LAD stricto sensu.

 
  References Top

1.Daoud MS, Lust JA, Kyle RA, Pittelkow MR. Monoclonal gammopathies and associated skin disorders. J Am Acad Dermatol 1999;40:507-35.  Back to cited text no. 1
[PUBMED]    
2.Wong DA, Hunt MJ, Stapleton K. IgA multiple myeloma presenting as an acquired bullous disorder. Australas J Dermatol 1999;40:31-4.  Back to cited text no. 2
[PUBMED]    
3.Barnadas MA, Gelpí C, Martínez L, Curell R, Martino R, Alomar A. Acquired bullous dermatosis associated with IgA multiple myeloma: A case report. J Cutan Pathol 2010;37:1174-7.  Back to cited text no. 3
    
4.le Roux-Villet C, Prost-Squarcioni C, Sassolas B, Caux F, Flageul B, Lièvre N, et al. IgM bullous disease associated with IgM gammopathy: A report of two cases and review. Br J Dermatol 2004;150:392-4.  Back to cited text no. 4
    
5.Pas HH, Kloosterhuis GJ, Heeres K, van der Meer JB, Jonkman MF. Bullous pemphigoid and linear IgA dermatosis sera recognize a similar 120-kDa keratinocyte collagenous glycoprotein with antigenic cross-reactivity to BP180. J Invest Dermatol 1997;108:423-9.  Back to cited text no. 5
[PUBMED]    


    Figures

  [Figure 1], [Figure 2], [Figure 3]

This article has been cited by
1 Recurrent Subepidermal Blistering Dermatosis Heralding Disease Relapse in IgA Kappa Multiple Myeloma: Report of a Case and a Review of the Literature
Hayley W. Leatham,Roberto Novoa,Michaela Liedtke,Bernice Y. Kwong
Clinical Lymphoma Myeloma and Leukemia. 2016; 16(1): e1
[Pubmed] | [DOI]



 

Top
Print this article  Email this article

    

Online since 15th March '04
Published by Wolters Kluwer - Medknow