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Advances in dermatology and venereology Acta Dermato-Venereologica
Linear IgA Bullous Dermatosis in a Pregnant Woman with Autoantibodies to the Non-collagenous 16A Domain of Type XVII Collagen
Kenshi MATSUURA 1 , Hideyuki UJIIE 1 *, Masahiro HAYASHI 2 , Ken MURAMATSU 1 , Junko YOSHIZAWA 2 , Takamasa ITO 1 , Hiroaki IWATA 1 , Tamio SUZUKI 2 and Hiroshi SHIMIZU 1 Departments of Dermatology , 1 Hokkaido University Graduate School of Medicine , North 15 West 7 , Kita-ku , Sapporo 060-8638 , Sapporo , and 2 Yamagata University School of Medicine , Yamagata , Japan . * E-mail : h-ujiie @ med . hokudai . ac . jp Accepted Oct 26 , 2016 ; Epub ahead of print Oct 27 , 2016
Linear IgA bullous dermatosis ( LABD ) is a rare subepidermal autoimmune blistering disorder in which IgA autoantibodies to the 120-kDa and 97-kDa shed ectodomains of type XVII collagen ( COL17 , BP180 ) at the basement membrane zone ( BMZ ) are most frequently detected ( 1 , 2 ). The aetiology of LABD remains largely unclear , although associations with drugs , infections and malignancies have been reported ( 1 ). As only a few cases of LABD in pregnancy have been reported ( 3 ), little is known about the aetiology of such cases . We report here the first case of LABD in a pregnant woman , in which the target epitope of the autoantibodies was identified as the non-collagenous 16A ( NC16A ) domain of COL17 .
CASE REPORT
A 29-year-old woman at 38 weeks of her first pregnancy showed a 3-week history of painful pruritic eruptions on the trunk , extremities and lips . The patient had no significant medical history . Physical examination revealed numerous erythematous plaques up to 3 cm in diameter associated with tense blisters in annular arrays on the extremities , abdomen and buttocks ( Fig . 1A , B ). The mucous membranes were intact , except for multiple erosions on the lips . Serum levels of IgG autoantibodies to desmoglein ( Dsg ) 1 , Dsg3 , and the NC16A domain of COL17 measured by chemiluminescent enzyme immunoassay ( CLEIA ) were not detectable . Histopathologically , a tense blister on the left forearm exhibited subepidermal separation with a mild infiltration of lymphocytes and neutrophils ( Fig . 1C ). Direct immunofluorescence ( DIF ) revealed the linear deposition of IgA ( Fig . 1D ), but not of IgG , IgM or C3 at the BMZ . Indirect immunofluorescence ( IIF ) for the serum also showed linear deposition of IgA at the BMZ at 8 × dilution ( Fig . 1E ). 1M NaCl-split-skin IIF was positive for IgA on the epidermal side ( Fig . 1F ). Based on these findings , a diagnosis of LABD in pregnancy was made . To identify the autoantigen that is targeted by the IgA autoantibody , we performed further analyses by Western blotting and enzyme-linked immunoassay ( ELISA ). Western blotting using a culture supernatant of HaCaT cells and epidermal extracts from a healthy control individual was negative for IgA ( Fig . 1G ). However , Western blotting using the recombinant NC16A domain of COL17 was weakly positive for IgA ( Fig . 1H ). By COL17 NC16A ELISA ( MBL , Nagoya , Japan ) using 1:101 diluted sera and 1:10000 diluted polyclonal rabbit anti-human IgA ( Dako , Glostrup , Denmark ) as a secondary antibody , the optical density 450 nm ( OD 450 ) in our patient ’ s serum was significantly higher than that in the sera of normal controls ( 0.69 ± 0.05 vs . 0.03 ± 0.0003 , p < 0.0001 ). Thus , the circulating IgA autoantibodies in our case were found to react with the NC16A domain , but not with the 120-kDa ( LAD-1 ) shed ectodomains , of COL17 . Oral prednisolone , 20 mg / day ( 0.3 mg / kg / day ), was administered , but new skin lesions continued to appear . Increasing the dose of oral prednisolone to 30 mg / day ( 0.5 mg / kg / day ) led to remission . Her delivery was without complications , and her baby showed neither erythema nor blisters . The oral prednisolone was gradually tapered to 12 mg / day over the course of 2 months after delivery , with a mild relapse of vesicles on the extremities .
The closest differential diagnosis of our case was pemphigoid gestationis ( PG ), the most common autoimmune subepidermal blistering disorder in pregnancy . The clinical features of PG , such as pruritic urticarial plaques and annularly distributed vesicles , are similar to those of LABD and of our case . In PG , dermal infiltration of eosinophils is common and linear deposition of C3 ± IgG at the BMZ must be observed in perilesional skin by DIF ( 4 ). Due to the absence of these findings , we distinguished PG from our case .
DISCUSSION
LABD in pregnancy has rarely been reported . According to a case series of LABD in pregnancy , the disease usually improves by the end of the first trimester ( 3 ). In only one case did the patient experience serious problems during labour and blister formation on the neonate ( 3 ). A relapse occurred in 75 % of patients within 4 months after delivery , and it was usually worse than the initial episode and required an increased dose of medication ( 3 ). As our patient still shows new skin lesions even with oral predonisolone at 15 mg / day , we should carefully follow up the patient .
To our knowledge , this is the first case of LABD in pregnancy in which the autoantigen was identified . Interestingly , the circulating autoantibodies in our case targeted the NC16A domain of COL17 , but not the 120-kDa shed ectodomains of COL17 , which is a common autoantigen in LABD . Although shed ectodomains of COL17 are known to be the major autoantigens of LABD , it has been reported that IgA autoantibodies in 22 % of LABD cases can react to the NC16A domain of COL17 ( 5 , 6 ). The vast majority of IgG autoantibodies react to the NC16A domain of COL17 in PG cases ( 7 ). Although the precise pathomechanism of PG has not been fully elucidated , aberrantly expressed human leukocyte antigen ( HLA ) class II molecules in the placenta , certain HLA types , and hormones , such as oestrogen and progesterone , are considered to be relevant to a breakdown of the immunological tolerance of the mother to the fetoplacental unit , which results in the production of IgG autoantibodies to the NC16A domain of COL17 ( 8 , 9 ). We presumed that PG and LABD in pregnancy have overlapping pathomechanisms that may explain why doi : 10.2340 / 00015555-2557 Acta Derm Venereol 2017 ; 97 : 404 – 405
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2017 Acta Dermato-Venereologica .