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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 21  |  Issue : 4  |  Page : 310-312

Mixed immunobullous disease in infants: Falls in bullous pemphigoid-linear IgA spectrum?


1 Department of Dermatology, Amala Institute of Medical Sciences, Thrissur, Kerala, India
2 Department of Pathology, Amala Institute of Medical Sciences, Thrissur, Kerala, India

Date of Submission11-Mar-2020
Date of Decision16-Mar-2020
Date of Acceptance14-Apr-2020
Date of Web Publication30-Sep-2020

Correspondence Address:
Dr. Sebastian Criton
Department of Dermatology, Amala Institute of Medical Sciences, Thrissur - 680 555, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_40_20

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  Abstract 


Bullous pemphigoid (BP) and linear immunoglobulin A bullous dermatosis (LABD) are common immunobullous diseases affecting both adults and children, with minor differences in clinical presentation. The only test for a definitive diagnosis is direct immunofluorescence (DIF) study, with linear deposits of immunoglobulin G (IgG) (mainly) at the dermoepidermal junction (DEJ) being diagnosed as BP and linear deposits of IgA at DEJ, diagnosed as LABD. Mixed immunobullous disease is the term given for immunobullous diseases with equal IgA/IgG deposits at the DEJ. Through this case report, a mixed immunobullous disease with clinical diagnosis of LABD and DIF findings of BP is being discussed. Furthermore, the presence of a BP-LABD spectrum of disease that can progress in either direction and present with features of both diseases is discussed.

Keywords: Bullous pemphigoid, linear immunoglobulin A bullous dermatosis, mixed immunobullous disease


How to cite this article:
Mohanan S, Criton S, Abraham UM. Mixed immunobullous disease in infants: Falls in bullous pemphigoid-linear IgA spectrum?. Indian J Paediatr Dermatol 2020;21:310-2

How to cite this URL:
Mohanan S, Criton S, Abraham UM. Mixed immunobullous disease in infants: Falls in bullous pemphigoid-linear IgA spectrum?. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 Oct 28];21:310-2. Available from: https://www.ijpd.in/text.asp?2020/21/4/310/296859




  Introduction Top


Mixed immunobullous disease is described as an immunobullous disease with equal immunoglobulin A (IgA) and IgG deposits at the dermoepidermal junction (DEJ) on immunofluorescence.[1]

Bullous pemphigoid (BP) is characterized by the presence of autoantibodies against BP180 or BP230. On direct immunofluorescence (DIF), predominant linear deposits of IgG and C3 are noted at DEJ, and rarely, other Ig subclasses.[2]

Linear IgA bullous dermatosis (LABD) is characterized by the presence of autoantibodies against LAD antigen/BP180/BP230. DIF shows exclusive or predominant IgA deposits at the DEJ, with rare presence of IgG deposits.[1],[2]

In this report, a rare case of an infant is being discussed, who clinically appeared to have linear IgA disease, but DIF showed predominant deposition of IgG and C3 at the DEJ, with faint positive IgA.


  Case Report Top


A 4-month-old female baby was brought to the dermatology outpatient department, with complaints of multiple clear blisters over the body. The child who was asymptomatic 1 week prior developed few erythematous plaques over the hands and feet. Clear grouped blisters appeared over these plaques, which coalesced, forming large, tense bullae. There was rapid involvement of the perineum, under the surface of the chin, and the nape of the neck within 2 days. Bullae ruptured in a day, leaving erosions that healed without scarring. The mucosa was not involved. There was a history of cough 2 weeks before the onset of blisters, which was treated with paracetamol and salbutamol. There was no history of consanguinity, trauma, photosensitivity, or similar lesions in the family. She was born with an atrial septal defect-ostium secundum type.

General and systemic examinations were unremarkable. On dermatologic examination, there were clear, tense bullae over the bilateral palms, dorsum of the hands, bilateral feet, chin, the nape of the neck, umbilicus, and the labia majora. Bulla spread sign and Nikolsky sign were negative. Bullae were arranged in an annular pattern over an erythematous plaque, closer to the edges. Few erosions were observed in the right hand and both feet [Figure 1]a, [Figure 1]b, [Figure 1]c.
Figure 1: (a) Photograph of the left upper limb of the child at the time of admission. Black arrows point the bullae over annular plaques. (b) Photograph shows under the surface of the chin with blisters arranged in an annular pattern (black arrow). (c) Photograph showing blisters mainly arranged in annular pattern over erythematous base (black arrows)

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Complete blood count results were normal. Histopathology of the bulla showed a subepidermal blister with predominant eosinophils and few lymphocytes, with dermal perivascular infiltrate of eosinophils and lymphocytes [Figure 2]. DIF showed linear basement membrane zone (BMZ) deposits of IgG (3+), C3 (3+), IgA (1+), and IgM (negative) [Figure 2], [Figure 3], [Figure 4], [Figure 5].
Figure 2: High power ×40 view of histopathologic section of a bulla, showing subepidermal separation and mixed infiltrate of eosinophils and neutrophils within bullae. The dermis also shows lymphocytic infiltrates

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Figure 3: High power ×40 microscopic view of direct immunofluorescence of the perilesional skin, stained for immunoglobulin G antibody. White arrow marks the linear immunoglobulin G deposits along the basement membrane zone

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Figure 4: High power ×40 microscopic view of direct immunofluorescence of the perilesional skin, stained for immunoglobulin A antibody. White arrow marks the faint linear deposits of immunoglobulin A along the basement membrane zone. (better appreciated when compared with immunoglobulin M negative direct immunofluorescence image [Figure 5])

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Figure 5: High power ×40 microscopic view of direct immunofluorescence of the perilesional skin, stained for immunoglobulin M antibody. There were no deposits

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The child was treated with oral prednisolone 6 mg (0.1 mg/kg/day) and oral antibiotic. The existing bullae shrunk and no new lesions appeared; erosions healed, and the child became active and playful.


  Discussion Top


Vesiculobullous disorders are broadly classified as intraepidermal and subepidermal blistering diseases, based on the level of the split. Subepidermal blistering diseases are subclassified depending on the type of deposits along the DEJ – linear or granular. Among the linear deposition diseases are BP, linear IgA bullous dermatoses, mucous membrane pemphigoid, and epidermolysis bullosa acquisita.[1]

BP is usually seen in the elderly but can also affect the young. It presents as intensely itchy, tense, clear blisters over normal/erythematous skin. Histopathology reveals a subepidermal blister, and DIF shows predominant IgG and C3 deposits. When untreated, the disease undergoes a chronic self-limiting course with complete remission after 6 years in most patients.[1],[2]

LABD is typically seen in infants and children, with a clinical presentation of tense, clear blisters over the edge of annular erythematous plaques. Lesions tend to involve the perineum, perioral areas, and mucosa. A drug trigger can also initiate the disease, for example, nonsteroidal anti-inflammatory drugs, penicillins, infection, trauma, and vaccination being other triggers. Histopathology reveals a subepidermal blister, and DIF shows predominant linear deposits of IgA at the DEJ. Patients with LABD usually respond well to treatment, with complete remission within 2 years. Drug-induced LABD heals within 6–8 weeks after discontinuing the drug.[1],[2]

Recently, a new variant of immunobullous diseases is termed as mixed immunobullous disease.[1] There have been few case reports suggesting the overlap of BP and LABD in adults and children, with a clinical diagnosis of LABD and DIF findings of BP, or vice versa. No case reports showing such overlap in infants have been published yet.[3],[4] A study by Kirtsching et al.[3] had found the faint presence of IgA deposits in patients with BP. However, there were no IgA deposits in <1 year age.

Comparing the antibodies seen in BP and LABD has relevance in this context, correlating with the current concept of the “epitope spreading” phenomenon. It proposes that varied B- and T-cell responses in autoimmune blistering disease are due to widespread reaction to various epitopes present on the target antigenic proteins, i.e., antibodies are not epitope restricted.[5] In a study on BP patients, it was found that antibodies are initially produced against the extracellular domain of BP180, with later reaction to other epitopes within the intracellular domain of BP180 and to BP230.[4] This points to the presence of epitope spreading. A similar study on patients with LABD showed heterogeneous antigens stimulating antibody response.[6] If the predominant antibody is IgG, the disease is diagnosed as BP; a predominant IgA deposit makes the diagnosis LABD. An equal IgG/IgA linear deposit at BMZ points to mixed immunobullous disease.

Through this article, we would like to propose that BP-LAD is a spectral disease that can occur in any age group, and it is possible to progress the disease from one end of the spectrum to the other end, which may be explained by “epitope spreading.” This may explain the variable expression of IgG/IgA in BMZ. At this point of time, there are no evidences for this hypothesis. However, with the help of further genetic and molecular biological studies, it may be possible to prove this hypothesis.


  Conclusion Top


BP and LABD are separate types of immunobullous disease. However, it is observed that there exists a spectrum of diseases that have an overlap of features of both these diseases, mixed immunobullous disease lying at the midpoint. Regarding the follow-up of the case discussed here, the child responded well to systemic steroids. The prognosis of such diseases and other treatment options are yet to be determined.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Schmidt E, Groves R. Immunobullous disease. In: Griffiths CE, editor. Rook's Textbook of Dermatology. 9th ed., Vol. 2. UK: John Wiley & Sons Ltd.; 2016. p. 50.10-50.37.  Back to cited text no. 1
    
2.
Bernard P, Borradori L. Pemphigoid group. In: Bolognia JL, editor. Dermatology. 4th ed., Vol. 1. China: Elsevier Limited; 2018. p. 510-8, 533-6.  Back to cited text no. 2
    
3.
Kirtschig G, Wojnarowska F. IgA basement membrane zone autoantibodies in bullous pemphigoid detect epidermal antigens of 270-280 kDa, 230 kDa, and 180 kDa molecular weight by immunoblotting. Clin Exp Dermatol 1999;24:302-7.  Back to cited text no. 3
    
4.
Haneef NS, Ramachandra S, Metta AK, Srujana L. Chronic bullous disease of childhood with IgG predominance: What is the locus standi? Indian J Dermatol 2012;57:285-7.  Back to cited text no. 4
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5.
Di Zenzo G, Thoma-Uszynski S, Calabresi V, Fontao L, Hofmann SC, Lacour JP, et al. Demonstration of epitope-spreading phenomena in bullous pemphigoid: Results of a prospective multicenter study. J Invest Dermatol 2011;131:2271-80.  Back to cited text no. 5
    
6.
Ohata C, Ishii N, Koga H, Nakama T. A clinical and serological study of linear IgA bullous dermatosis without linear immunoglobulin deposition other than IgA at the basement membrane zone using direct immunofluorescence. Br J Dermatol 2017;177:152-7.  Back to cited text no. 6
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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