• Users Online: 431
  • Print this page
  • Email this page


 
 
Table of Contents
CASE REPORT
Year : 2019  |  Volume : 37  |  Issue : 4  |  Page : 226-228

IgG/IgA pemphigus presenting with mixed clinical features of pemphigus erythematosus and IgA pemphigus


1 Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung; College of Medicine, Chang Gung University, Taoyuan, Taiwan
2 Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan

Date of Submission27-Dec-2018
Date of Decision23-Feb-2019
Date of Acceptance19-Mar-2019
Date of Web Publication16-Dec-2019

Correspondence Address:
Dr. Chun-Bing Chen
Department of Dermatology, Chang Gung Memorial Hospital, Keelung Branch, No. 222, Maijin Road, Anle District, Keelung City

Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ds.ds_12_19

Rights and Permissions
  Abstract 


IgG/IgA pemphigus is a phenotype of atypical pemphigus with variable clinical, histological, and immunological manifestations. We describe a unique case of IgG/IgA pemphigus in a 58-year-old male presenting with mixed features of pemphigus erythematosus and IgA pemphigus. The diagnosis is made based on the histopathological examination and intercellular deposition of IgG and IgA throughout the epidermis on direct immunofluorescence test. The patient responded favorably to the combination therapy of dapsone and low-dose systemic steroids.

Keywords: Autoimmune bullous diseases, IgA pemphigus, IgG/IgA pemphigus, pemphigus erythematosus


How to cite this article:
Yang SJ, Lee HE, Chang CH, Chen CB. IgG/IgA pemphigus presenting with mixed clinical features of pemphigus erythematosus and IgA pemphigus. Dermatol Sin 2019;37:226-8

How to cite this URL:
Yang SJ, Lee HE, Chang CH, Chen CB. IgG/IgA pemphigus presenting with mixed clinical features of pemphigus erythematosus and IgA pemphigus. Dermatol Sin [serial online] 2019 [cited 2020 Aug 15];37:226-8. Available from: http://www.dermsinica.org/text.asp?2019/37/4/226/273095




  Introduction Top


Pemphigus is a group of autoimmune bullous diseases characterized by autoantibodies targeting intercellular components of the epidermis. Pemphigus vulgaris and pemphigus foliaceus are the two major subtypes of pemphigus: they are caused by IgG antibodies against desmoglein-3 (Dsg-3) and desmoglein-1 (Dsg-1), respectively. Paraneoplastic pemphigus, pemphigus herpetiformis, and IgA pemphigus are less common forms of pemphigus. IgG/IgA pemphigus is another relatively newly described atypical form of pemphigus and manifested with variable clinical features. Herein, we reported a unique case of IgG/IgA pemphigus with mixed features of pemphigus erythematosus and IgA pemphigus.


  Case Report Top


A 58-year-old male developed progressive skin lesions with mild pruritus for 9 months. The lesions were initially noted as red macules and patches with blister and/or pustule formation on the chest and gradually spread to the abdomen, back, neck, face, scalp, and limbs despite receiving treatment with topical steroid and oral antihistamine at local clinics. Physical examination revealed multiple annular erythematous maculopatches with crusted erosions and scattered pustules on the trunk and patches of erythema on the forehead, nose, and cheeks like a malar rash [Figure 1]. There was no mucosal involvement. The results of initial laboratory tests, including complete blood count, renal function, and liver function, were within normal limits. Test for antinuclear antibody produced negative result. The C3 level was within normal range (111.00; normal, 79–152 mg/dl), and the C4 level was mildly decreased (15.50; normal, 16–38 mg/dL).
Figure 1: (a) Multiple annular erythematous maculopatches with crusted erosions and scattered pustules on the trunk. (b) Erythematous rash over the malar region sparing the nasolabial folds. (c) Close-up view of the lesions on the abdomen

Click here to view


Skin biopsy of the lesion located on the abdomen showed subcorneal pustules containing neutrophils and superficial acantholytic cells [Figure 2]a. Acantholytic granular cells in the infundibular portion of one hair follicle were also found [Figure 2]b. Direct immunofluorescence (DIF) revealed intercellular deposits of IgA, IgG, and C3 throughout the epidermis, and there was no deposition at the basement membrane zone [Figure 2]c and [Figure 2]d. To determine the anti-Dsg1 and anti-Dsg3 IgG titers, enzyme-linked immunosorbent assay (ELISA) for detecting IgG antibodies to Dsg1 and Dsg3 was performed with 1:100 diluted serum samples according to the manufacturer's instructions. Anti-Dsg1 was positive with 80.00 U/ml, and anti-Dsg3 was negative with 0.03 U/ml (the cutoff values proposed by the manufacturer were 20 U/mL for anti-Dsg1 antibody and 14 U/mL for anti-Dsg3 antibody). Thus, a diagnosis of IgG/IgA pemphigus was established.
Figure 2: (a) Subcorneal pustules containing neutrophils and superficial acantholytic cells (H and E, ×100). (b) Acantholytic granular cells in the infundibular portion of a hair follicle (H and E, ×100). (c and d) Intercellular deposits of IgG and IgA throughout the epidermis on direct immunofluorescence (×100)

Click here to view


The patient was initially treated with methylprednisolone (prednisolone equivalent dosage: 0.3 mg/kg/day), and the skin lesions got mild improved within 3 weeks. Dapsone 100 mg/day was then added and the patient showed good response. The dose of methylprednisolone was tapered quickly to 2–4 mg per day. However, the dapsone was discontinued 4 months later because the patient developed hemolytic anemia despite the fact that he had a normal G6PD level. The skin lesions recurred after discontinuation of dapsone.


  Discussion Top


IgG/IgA pemphigus, a rare subtype of pemphigus, is characterized by intercellular deposits of both IgG and IgA in the epidermis. The manifestation of reported IgG/IgA pemphigus cases is variable. The clinical appearance may resemble other subtypes of pemphigus, such as pemphigus vulgaris, pemphigus foliaceus, pemphigus herpetiformis, or IgA pemphigus; it may also present with mixed or atypical features.[1] Whether IgG/IgA pemphigus is a distinct clinical entity is still under debate. Toosi et al. analyzed 13 patients with IgG/IgA pemphigus and compared their disease feature to those of IgG pemphigus and IgA pemphigus, and they found that the presentation of IgG/IgA pemphigus is very similar to IgG pemphigus and distinct from IgA pemphigus.[2] They concluded that IgG/IgA pemphigus may be viewed as a variant of IgG pemphigus. However, in the largest case series to date including 30 patients, Hashimoto et al. reported that their cases tended to show mixed features of IgG pemphigus and IgA pemphigus.[3] They introduced a new term “intercellular IgG/IgA dermatosis” for this disorder and concluded that it is a distinct entity. On the other hand, it has been reported that IgG deposition on DIF may be found in some cases of IgA pemphigus.[4] It is possible that IgG/IgA pemphigus represents a spectrum of disease with overlapping clinical, histological, and immunophenotypic characteristics, with pure IgG pemphigus at one end and pure IgA pemphigus at the other. It is worth noting that cases of IgG/IgA pemphigus without IgA cell surface deposition on DIF or indirect immunofluorescence but with circulating IgA Dsg1 and Dsg3 antibodies by ELISA have been reported.[5] Because IgA ELISA assays are not widely available in routine clinical practice, IgG/IgA pemphigus might be more common than previously thought.

Our case presented with overlapping features of pemphigus erythematosus and IgA pemphigus. Pemphigus erythematosus is a rare form of pemphigus foliaceus characterized by an erythematous rash with scaling and crusting localized to the malar region of the face resembling lupus erythematosus. IgG/IgA pemphigus with malar rash-like erythema, as in our case, is seldom reported in the literature.[6] The rash on the trunk of our case has more features of IgA pemphigus, namely the annular configuration and presence of pustules.

A special concern about IgG/IgA pemphigus is its possible association with malignancy. While Bunimovich et al. stated that approximately one-third of reported IgG/IgA pemphigus cases were associated with malignancy,[7] the true prevalence remains unclear. Several types of neoplasm associated with this entity have been reported, including lung cancer,[7],[8],[9] ovarian carcinoma,[10] carcinoma of gallbladder,[11] adenocarcinoma in situ of the pancreas,[12] endometrial cancer,[13] and thymoma.[14] Association with monoclonal IgA gammopathy has also been reported.[15] In contrast to paraneoplastic pemphigus, which is most commonly induced by lymphoproliferative disorders, most of the reported malignancies associated with IgG/IgA pemphigus are solid tumors. We arranged cancer screening for our case with whole-body computed tomography, and no tumor was found. Serum protein electrophoresis showed no evidence of monoclonal gammopathy.

The optimal treatment for IgG/IgA pemphigus remains undefined. Dapsone, systemic steroid, minocycline, retinoids, topical steroid, and combination of these drugs have been used to treat IgG/IgA pemphigus with variable response.[3],[16] While the prognosis is considered to be favorable by most authors,[14] Toosi et al. found that most patients required moderate-to-high doses of systemic steroids to achieve disease control.[2] Our case showed good response to dapsone and low-dose systemic steroids. However, relapse was noted following discontinuation of dapsone.

In conclusion, we reported a case of IgG/IgA pemphigus presenting with overlapping features of pemphigus erythematosus and IgA pemphigus. The use of dapsone in combination with low-dose systemic steroids has a good therapeutic effect.

Ethical statement

The study participant provided written informed consent to participate in the study, which was approved by the Institutional Review Board of Chang Gung Medical Foundation, in compliance with Taiwanese law (IRB no. 201801725B0).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest



 
  References Top

1.
Porro AM, Caetano Lde V, Maehara Lde S, Enokihara MM. Non-classical forms of pemphigus: Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus. An Bras Dermatol 2014;89:96-106.  Back to cited text no. 1
    
2.
Toosi S, Collins JW, Lohse CM, Wolz MM, Wieland CN, Camilleri MJ, et al. Clinicopathologic features of IgG/IgA pemphigus in comparison with classic (IgG) and IgA pemphigus. Int J Dermatol 2016;55:e184-90.  Back to cited text no. 2
    
3.
Hashimoto T, Teye K, Hashimoto K, Wozniak K, Ueo D, Fujiwara S, et al. Clinical and immunological study of 30 cases with both IgG and IgA anti-keratinocyte cell surface autoantibodies toward the definition of intercellular IgG/IgA dermatosis. Front Immunol 2018;9:994.  Back to cited text no. 3
    
4.
Tsuruta D, Ishii N, Hamada T, Ohyama B, Fukuda S, Koga H, et al. IgA pemphigus. Clin Dermatol 2011;29:437-42.  Back to cited text no. 4
    
5.
Mentink LF, de Jong MC, Kloosterhuis GJ, Zuiderveen J, Jonkman MF, Pas HH. Coexistence of IgA antibodies to desmogleins 1 and 3 in pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus. Br J Dermatol 2007;156:635-41.  Back to cited text no. 5
    
6.
Hosoda S, Suzuki M, Komine M, Murata S, Hashimoto T, Ohtsuki M. A case of IgG/IgA pemphigus presenting malar rash-like erythema. Acta Derm Venereol 2012;92:164-6.  Back to cited text no. 6
    
7.
Bunimovich Y, Teye K, Ishii N, Ho J, Hashimoto T. IgG/IgA pemphigus with autoantibodies to desmoglein 1 and desmocollin 3, and associated lung cancer. J Clin Cosmet Dermatol 2016;1:doi http://dx.doi.org/10.16966/2576-2826.102.  Back to cited text no. 7
    
8.
Chorzelski TP, Hashimoto T, Nishikawa T, Ebihara T, Dmochowski M, Ismail M, et al. Unusual acantholytic bullous dermatosis associated with neoplasia and IgG and IgA antibodies against bovine desmocollins I and II. J Am Acad Dermatol 1994;31:351-5.  Back to cited text no. 8
    
9.
Cetkovská P, Komorousová M, Lomicová I. Management of a pemphigus with IgA and IgG antibodies and coexistent lung cancer. Dermatol Ther 2014;27:236-9.  Back to cited text no. 9
    
10.
Kowalewski C, Hashimoto T, Amagai M, Jablonska S, Mackiewicz W, Wozniak K. IgA/IgG pemphigus: A new atypical subset of pemphigus? Acta Derm Venereol 2006;86:357-8.  Back to cited text no. 10
    
11.
Maruyama H, Kawachi Y, Fujisawa Y, Itoh S, Furuta J, Ishii Y, et al. IgA/IgG pemphigus positive for anti-desmoglein 1 autoantibody. Eur J Dermatol 2007;17:94-5.  Back to cited text no. 11
    
12.
Santiago-et-Sánchez-Mateos D, Juárez Martín A, González De Arriba A, Delgado Jiménez Y, Fraga J, Hashimoto T, et al. IgG/IgA pemphigus with IgA and IgG antidesmoglein 1 antibodies detected by enzyme-linked immunosorbent assay: Presentation of two cases. J Eur Acad Dermatol Venereol 2011;25:110-2.  Back to cited text no. 12
    
13.
Lane N, Parekh P. IgG/IgA pemphigus. Am J Dermatopathol 2014;36:1002-4.  Back to cited text no. 13
    
14.
Reichel A, Benoit S, Giner T, Schmidt E, Goebeler M, Stoevesandt J. Anti-desmoglein 1 IgG/IgA pemphigus associated with thymoma. J Dtsch Dermatol Ges 2017;15:1147-8.  Back to cited text no. 14
    
15.
Miyagawa S, Hashimoto T, Ohno H, Nakagawa A, Watanabe K, Nishikawa T, et al. Atypical pemphigus associated with monoclonal IgA gammopathy. J Am Acad Dermatol 1995;32:352-7.  Back to cited text no. 15
    
16.
Watkins C, West C, Kosari P, Ali S, Sangüeza O, Huang W. IgG/IgA pemphigus: Report of a rare variant of atypical pemphigus and a review of the literature. J Dermatolog Clin Res 2014;2:1011.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Case Report
Discussion
References
Article Figures

 Article Access Statistics
    Viewed449    
    Printed33    
    Emailed0    
    PDF Downloaded86    
    Comments [Add]    

Recommend this journal