|Year : 2019 | Volume
| Issue : 4 | Page : 226-228
IgG/IgA pemphigus presenting with mixed clinical features of pemphigus erythematosus and IgA pemphigus
Shih-Jyun Yang1, Hua-En Lee1, Chih-Hao Chang1, Chun-Bing Chen2
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 Submission||27-Dec-2018|
|Date of Decision||23-Feb-2019|
|Date of Acceptance||19-Mar-2019|
|Date of Web Publication||16-Dec-2019|
Dr. Chun-Bing Chen
Department of Dermatology, Chang Gung Memorial Hospital, Keelung Branch, No. 222, Maijin Road, Anle District, Keelung City
Source of Support: None, Conflict of Interest: None
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 Jul 10];37:226-8. Available from: http://www.dermsinica.org/text.asp?2019/37/4/226/273095
| Introduction|| |
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|| |
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|
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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)|
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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|| |
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. 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. 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. 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. 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. 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. 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, the true prevalence remains unclear. Several types of neoplasm associated with this entity have been reported, including lung cancer,,, ovarian carcinoma, carcinoma of gallbladder, adenocarcinoma in situ of the pancreas, endometrial cancer, and thymoma. Association with monoclonal IgA gammopathy has also been reported. 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., While the prognosis is considered to be favorable by most authors, Toosi et al. found that most patients required moderate-to-high doses of systemic steroids to achieve disease control. 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.
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
Conflicts of interest
There are no conflicts of interest
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[Figure 1], [Figure 2]