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Two cases of childhood bullous pemphigoid

European Journal of Dermatology. Volume 19, Number 4, 368-71, July-August 2009, Clinical report

DOI : 10.1684/ejd.2009.0694

Summary

Author(s) : Tomoko Toyama, Koichiro Nakamura, Akira Kuramochi, Bungo Ohyama, Takashi Hashimoto, Tetsuya Tsuchida , Department of Dermatology, Saitama Medical University, 38 Morohongo, Moroyamamachi, Iruma-gun, Saitama, Japan, 350-0495, Department of Dermatology, 67 Asahi-machi, Kurume, Fukuoka, Japan, 830-0011.

Summary : This report describes two cases of childhood bullous pemphigoid (BP). These cases showed vesiculobullous lesions on the face, trunk, extremities, hands and feet. Histopathological analysis of skin lesions showed infiltration of numerous lymphocytes and eosinophils in the superficial dermis. Immunofluorescent analysis showed a linear IgG deposit along the basement membrane zone. In both cases ELISA showed circulating IgG autoantibodies against the NC16A domain of 180-KDa BP antigen (BP180). Both IgG and IgA (faint deposit) autoantibodies against the NC16A domain of BP180 were detected by an immunoblot analysis in both cases. Both patients showed a similar clinical course with a rapid remission after treatment with topical corticosteroids. Both patients received vaccinations within two weeks before the appearance of the eruption. These cases were considered to be childhood BP presenting both IgG and IgA autoantibodies against the NC16A domains of BP180.

Keywords : bullous pemphigoid, childhood, NC16A, BP180

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Auteur(s) : Tomoko Toyama¹, Koichiro Nakamura¹, Akira Kuramochi¹, Bungo Ohyama², Takashi Hashimoto², Tetsuya Tsuchida¹

¹Department of Dermatology, Saitama Medical University, 38 Morohongo, Moroyamamachi, Iruma-gun, Saitama, Japan, 350-0495
²Department of Dermatology, 67 Asahi-machi, Kurume, Fukuoka, Japan, 830-0011

accepté le 25 Février 2009

Childhood bullous pemphigoid (BP) is a rare IgG-mediated subepidermal blistering disease in children [1]. The clinical features of childhood BP are clinically similar to those of adult BP and often characterized by the involvement of palms and soles [2]. Childhood BP is diagnosed on the following critera: patients younger than 18 years old, the clinical finding of blisters or vesiculobullae with no scarring, and IgG autoantibodies against the basement membrane zone (BMZ), detected by a direct immunofluorescent analysis [1]. Recent evidence has shown that an immunoblot assay or ELISA testing demonstrates circulating autoantibodies against 180 KDa BP antigen (BP 180) and 230 KDa BP antigen (BP230) in childhood BP [3-6]. This paper reports two cases of childhood BP presenting both IgG and IgA autoantibodies against the NC16A domain of BP180.

Case 1

A 5-month-old girl developed a sudden eruption of bullae and blisters on her feet in July 2007. The eruption quickly generalized in her extremities and trunk. She was referred to the hospital in August 2007. A physical examination revealed that she had an eruption of tense blisters and vesicles with surrounding erythema on her trunk, extremities, hands and feet (figures 1 A-D). No mucosal involvement was detected. Three days before the appearance of the eruption she had received a vaccination for diphtheria-tetanus-acellular pertussis. A histological examination of the erythema on her trunk showed perivascular lymphocyte and eosinophil infiltrations in the superficial dermis (figures 1E, F). Laboratory findings showed an increased white blood cell count (16,330/μL), eosinophils (18.7%), platelet counts (4.75 × 10⁴/μL), CRP (0.26 mg/dL), AST(46 IU/L), LDH (300 IU/L) and ALP (524 IU/L). A direct immunofluorescent (DIF) examination showed a linear deposit of IgG, IgM and C3 along the BMZ (figures 1G, H). The titer of IgG antibodies against the NC16A domain was over 150 by ELISA (cut off index: 9). An immunoblot analysis of serum samples from the patient showed positive IgG and IgA (faint deposit) autoantibodies against the NC16A domain of BP180 (figure 3A). She was treated with topical corticosteroid (hydrocortisone butylate propionate) ointment twice a day on the erythema and vesiculobullous lesions on the trunk and extremities. The eruption resolved within 2 weeks and topical corticosteroids were continued once a day. A complete remission was observed within 2 months of the treatment. Since October 2007 no new eruption has been seen. ELISA for IgG autoantibodies against the NC16A domain showed negative titers (index: 9) 6 months after cessation of the eruption.

Case 2

A 5-month-old girl developed tense blisters and vesicles on her feet in August 2007. On the next day the eruption quickly spread to her face, fingers, trunk and extremities. She was referred to the hospital in September 2007. A physical examination revealed that there were lesions on her face, palms, soles, trunk and extremities (figures 2A-D). No mucosal involvement was detected. A histological examination of erythema on her trunk revealed infiltration of lymphocytes and eosinophils in the superficial dermis (figure 2E). DIF of the perilesional skin revealed linear intense staining of IgG along the BMZ. IF using sodium chloride-treated split skin showed intense IgG and IgA deposition along the upper parts of the separated BMZ (figures 2F, G). Laboratory findings showed increased levels of white blood cells (10,530/μL), eosinophils (7.7%), AST (40 IU/L), CRP (0.26 mg/dL) and LDH (257 IU/L). ELISA showed high titers of IgG autoantibodies (index: 107.6) against the NC16A domain of BP180 in this patient. An immunoblot analysis showed both IgG and IgA (faint positive) deposits against the NC16A region of BP180 (figure 3 B). She had received a vaccination against bacille Calmette-Guerin (BCG) 9 days before the appearance of the eruptions. After one week of topical corticosteroids (clobetasol propionate) twice a day on the trunk and extremities, the vesiculobullous lesions completely ceased and finally disappeared within one month. No recurrence has been detected after 6 months of follow-up.

Discussion

Childhood BP is a rare subepidermal blistering disease with eosinophil infiltrations. DIF is characterized by the deposition of IgG and/or C3 and IgA along the BMZ in the perilesional skin in childhood BP. Indirect IF reveals IgG deposition in the epidermal site on the sodium chloride-treated split skin. The presence of autoantibodies against the NC16A region of BP180 is detected by ELISA testing of sera of childhood BP, similar to adult BP [4]. The current cases showed IgG and IgA deposits against BMZ by an immunofluorescent analysis, and showed the circulating BP180 autoantibodies by ELISA and immunoblot assay.

Interestingly, an immunoblot analysis of the current cases showed IgA class in addition to IgG class autoantibodies against the NC16A domain of BP160. It has been reported that patients with BP have both IgG and IgA autoantibodies against the NC16A domain in a small percentage of the investigated patients. In addition, approximately 10% of the patients reported with childhood BP showed IgA deposits by DIF [2, 4]. Pablo et al. suggested the possibility that immunological immaturity or frequent exposure to infections causes the presence of IgA mediated immune responses in childhood BP [7].

Vaccination sometimes precedes the onset of childhood BP [3, 8-13]. 9 cases of childhood BP occurred after vaccinations such as tetracoq (combined tetanus, diphtheria, Bordetella pertussis, and poliovirus), and hepatitis B vaccination. These cases showed similar clinical features to cases which developed without vaccination. The current cases received vaccinations for diphtheria-tetanus-acellular pertussis and BCG. These data suggest that vaccination modulated the immunological homeostasis in these infants. However, although there are many infants who receive various kinds of vaccination and despite the rare occurrence of childhood BP, it is still possible that there is an association between vaccination and childhood BP. Pablo et al. suggest that “the epitope spreading phenomenon’’ may cause autoantibody production without pathogenetic factors in these cases [7]. The fact that only a few hours to days (5 hrs to 2 weeks) passed before the onset of the disease after vaccination suggests the unlikeliness of specific immune responses in the occurrence of childhood BP by vaccination.

Next, in case 1, the titers of IgG class autoantibodies against the NC16A domain by ELISA diminished after the treatment, along with the complete remission of the eruption. A case of childhood BP with localized skin involvement was reported to show negative titers of IgG autoantibodies by ELISA [5]. From these data, there is a possibility that the titers of IgG autoantibodies reflect the disease activity of childhood BP, similarly to adult BP. However, 4 cases of childhood BP showed similar clinical responses in spite of different levels of autoantibodies [7]. Further examination will be required to elucidate the association between titers of autoantibodies by ELISA and the disease activity of childhood BP.

Childhood BP generally has a good prognosis and a rapid response to treatment such as systemic corticosteroids, diaminodiphenyl sulfone, cyclosporine and immunoglobulins [2, 3, 7-10, 14-17]. In most patients the remission is usually achieved within a few months. In our patients, case 1 responded well to topical corticosteroids alone, with no further recurrence even after the withdrawal of the treatment. Case 2 also showed a prompt response to one week of topical corticosteroids with no further recurrence. Therefore, these data indicate that some patients show a good prognosis with treatment such as topical corticosteroids, as previously described [4, 13, 18]. However, several cases have shown a slow response to the treatment and recurrence, even after the withdrawal of the systemic treatment [8, 19, 20]. As a result, further careful follow up will be still required in the present cases.

Two cases of childhood BP presenting IgG and IgA class autoantibodies against the NC16A domain of BP180 were herein described. The characteristic expression of the IgG and IgA autoantibodies against the NC16A domains and the past history of vaccination immediately before the onset of the eruption in these cases will provide clues for the understanding of the pathogenesis of childhood BP.

Acknowledgements

Financial support: none. Conflict of interest: none.

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